on all orders above $300.00

FREE Pills!

via4gra pills

for free with every order



Less than in your
local pharmacy

Search by letter:

Tofranil (Imipramine)

Rating of sales:          


Generic Tofranil is a member of the family of drugs called tricyclic antidepressants. Generic Tofranil is used to treat depression. Generic Tofranil is also used on a short-term basis, along with behavioral therapies, to treat bed-wetting in children aged 6 and older. Sometimes Generic Tofranil is prescribed to treat bulimia, attention deficit disorder in children, obsessive-compulsive disorder and panic disorder.

Other names for this medication:

Similar Products:
Pamelor, Norpramin, Silenor, Zonalon, Aventyl, Norpress, Elavil


Also known as:  Imipramine.


Generic Tofranil is used to treat depression. Generic Tofranil is also used on a short-term basis, along with behavioral therapies, to treat bed-wetting in children aged 6 and older. Sometimes Generic Tofranil is prescribed to treat bulimia, attention deficit disorder in children, obsessive-compulsive disorder and panic disorder.

Generic Tofranil is a member of the family of drugs called tricyclic antidepressants.

Tofranil is also known as Imipramine, Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil, Irmin, Janimine, Melipramin, Surplix, Antidep, Apo-Imipramine, Chrytemin, Daypress, Depsol, Ethipramine, Fronil, Imidol, Imimine, Imine, Imiprex, Imiprin, Impril, Medipramine, Melipramine, Mipralin, Novopramine, Primonil, Pryleugan, Sermonil, Sipramine, Talpramin, Tofnil, Tofranil-PM, Venefon.

Generic name of Generic Tofranil is Imipramine hydrochloride.

Brand names of Generic Tofranil are Tofranil, Tofranil-PM.


Take Generic Tofranil orally.

Take Generic Tofranil with or without food.

For adults

The usual starting dose is 75 mg a day. The maximum daily dose is 200 mg.

For children

Total daily dosages for children should not exceed 2.5 mg for each 2.2 pounds of the child's weight. Doses usually begin at 25 mg per day. This amount should be taken an hour before bedtime. If needed, this dose may be increased after 1 week to 50 mg (ages 6 through 11) or 75 mg (ages 12 and up), taken in one dose at bedtime or divided into 2 doses, 1 taken at mid-afternoon and 1 at bedtime.

Aged people

The usual dosage should start with 25 to 50 mg per day. The dose may be increased as necessary, but effective dosages usually do not exceed 100 mg a day.

If you want to achieve most effective results do not stop taking Generic Tofranil suddenly.


If you overdose Generic Tofranil and you don't feel good you should visit your doctor or health care provider immediately. Symptoms of Generic Tofranil overdosage: agitation, bluish skin, convulsions, difficulty breathing, dilated pupils, drowsiness, heart failure, high fever, involuntary writhing or jerky movements, irregular or rapid heartbeat, lack of coordination, low blood pressure, overactive reflexes, restlessness, rigid muscles, shock, stupor, sweating, vomiting.


Store at room temperature between 20 and 25 degrees C (68 and 77 degrees F) away from moisture and heat. Keep container tightly closed. Throw away any unused medicine after the expiration date. Keep out of the reach of children.

Side effects

The most common side effects associated with Tofranil are:

  • tofranil tablets 10mg
  • tofranil 200 mg
  • tofranil diet pill
  • tofranil drug interactions
  • tofranil drug class
  • tofranil buy canada
  • tofranil pm generic
  • tofranil 150 mg
  • recommended tofranil dosage
  • tofranil reviews anxiety
  • tofranil tabs
  • tofranil low dose
  • tofranil 35 mg
  • tofranil overdose
  • tofranil dosage information
  • tofranil brand
  • tofranil dosage forms
  • tofranil generic
  • tofranil 25 mg
  • tofranil drug information
  • tofranil 50 mg
  • tofranil reviews
  • tofranil online
  • tofranil 100 mg
  • tofranil medication information
  • tofranil 25mg medication
  • tofranil tablet
  • tofranil overdose symptoms
  • tofranil 300 mg
  • tofranil and alcohol
  • tofranil brand name
  • tofranil pm dosage
  • tofranil drug category
  • tofranil max dose
  • tofranil street drug
  • tofranil y alcohol
  • tofranil drug study
  • tofranil dosage
  • tofranil bedwetting reviews
  • tofranil 25mg tab
  • tofranil 5 mg
  • tofranil user reviews
  • tofranil tablets
  • tofranil mg
  • tofranil pm reviews
  • tofranil overdose death
  • tofranil 10 mg
  • tofranil drug
  • tofranil 75 mg
  • tofranil missed dose
  • tofranil medicine
  • tofranil with alcohol
  • tofranil syrup
  • tofranil drug classification
  • tofranil generic name
  • tofranil maximum dosage
  • tofranil medication
  • tofranil tablet uses
  • tofranil cost

Side effect occurrence does not only depend on medication you are taking, but also on your overall health and other factors.


Do not take Generic Tofranil if you are allergic to Generic Tofranil components.

Be very careful with Generic Tofranil if you are pregnant, planning to become pregnant, or are breast-feeding.

Do not take Generic Tofranil if you are recovering from a recent heart attack or take MAO inhibitors, such as the antidepressants Nardil and Parnate.

Be very careful with Generic Tofranil if you have diabetes, hypoglycemia, a history of mental disorders.

Be very careful with Generic Tofranil if you are taking albuterol (Proventil, Ventolin), antidepressants that act on serotonin, including Prozac, Paxil and Zoloft, antipsychotic drugs such as Mellaril and chlorpromazine, barbiturates such as Nembutal and Seconal, blood pressure medications such as Catapres, Carbamazepine (Tegretol), cimetidine (Tagamet), decongestants such as Sudafed, drugs that control spasms, such as Cogentin, Epinephrine (EpiPen), Flecainide (Tambocor), Guanethidine, Methylphenidate (Ritalin), Norepinephrine, other antidepressants such as Elavil and Pamelor, Phenytoin (Dilantin), Propafenone (Rythmol), Quinidine, thyroid medications such as Synthroid, tranquilizers and sleep aids such as Halcion, Xanax, and Valium.

Avoid alcohol.

Do not participate in any activities that require full alertness if you are unsure about your ability.

Try to stay out of the sun as much as possible.

It can be dangerous to stop Generic Tofranil taking suddenly.

tofranil tablets

There is little evidence that anxiolytics aid smoking cessation. Some antidepressants (bupropion and nortriptyline) can aid smoking cessation. It is not clear whether these effects are specific for individual drugs, or a class effect.

tofranil brand

Physiologically based pharmacokinetic (PBPK) models were developed for design and optimization of liposome therapy for treatment of overdoses of tricyclic antidepressants and local anesthetics. In vitro drug-binding data for pegylated, anionic liposomes and published mechanistic equations for partition coefficients were used to develop the models. The models were proven reliable through comparisons to intravenous data. The liposomes were predicted to be highly effective at treating amitriptyline overdoses, with reductions in the area under the concentration versus time curves (AUC) of 64% for the heart and brain. Peak heart and brain drug concentrations were predicted to drop by 20%. Bupivacaine AUC and peak concentration reductions were lower at 15.4% and 17.3%, respectively, for the heart and brain. The predicted pharmacokinetic profiles following liposome administration agreed well with data from clinical studies where protein fragments were administered to patients for overdose treatment. Published data on local cardiac function were used to relate the predicted concentrations in the body to local pharmacodynamic effects in the heart. While the results offer encouragement for future liposome therapies geared toward overdose, it is imperative to point out that animal experiments and phase I clinical trials are the next steps to ensuring the efficacy of the treatment.

tofranil tablets 10mg

In 14 patients by bilateral retroperitoneal lymph node dissection for nonseminoma tumors of the testes, several sexual functions before and after node dissection were compared. All patients had normal sexual function before the operation. After the operation, antegrade ejaculation was found to have disappeared completely in 12 patients, retrograde ejaculation was demonstrable in ten of these patients. In ten patients, antegrade ejaculation was restored after treatment with 25 mg imipramine twice daily by mouth. In the two patients who still showed antegrade ejaculation, albeit diminished, imipramine medication led to an increased number of spermatoza. During imipramine medication, the partners of five patients became pregnant. The preliminary conclusion from these findings is that ejaculation disorders, which most males develop after bilateral retroperitoneal lymph node dissection, can be successfully treated with daily oral doses of 25-50 mg imipramine in the majority of patients who still desire children.

tofranil reviews anxiety

The purpose of this work was to examine the number and function of alpha 2-adrenoceptors and the number of serotonin uptake sites in depressed patients and controls. Platelet alpha 2-adrenoceptors and platelet serotonin uptake sites were labelled with [3H]yohimbine and [3H]imipramine respectively. Central alpha 2-adrenoceptor function was assessed by growth hormone and other responses to challenge with the alpha 2-agonist clonidine. No overall difference in the binding parameters was observed between the control and depressed groups, but the results highlight the importance of drug-free interval, menopausal status and membrane protein concentration within the binding assays in the interpretation of such studies. The growth hormone response to clonidine tended to be blunted in depressed females and was significantly blunted in the subgroup of depressives who failed to suppress plasma cortisol concentrations in response to dexamethasone. Depressed subjects also showed a smaller decrease in diastolic blood pressure and a smaller increase in sedation than control subjects.

tofranil dosage forms

3H-Imipramine binding in relation to serotonergic function was studied in patients hospitalized following a suicide attempt. Comparison with a control group showed a highly significant difference in Bmax values. The results suggest, at least a posteriori, a biological alteration as the basis of suicidal behaviour. Although it is impossible to attribute a suicidal attempt to the alteration or to a predisposing pre-existent condition, this biological marker may be useful in evaluating suicidal risk and also short- and long-term prognosis.

tofranil maximum dosage

Chronic intraperitoneal administration of desipramine led to an extensive cumulation of the drug in brain and blood compared with that after a single dose treatment, while chronic treatment with desipramine by the oral route produced a brain concentration comparable with its level after a single oral dose. Comparison of the present results with the corresponding data of published imipramine pharmacokinetics indicated that the cumulation of desipramine in the rat brain was nearly the same when rats received desipramine or imipramine twice a day for two weeks at a dose of 10 mg kg-1 orally, or imipramine, twice a day for two weeks at a dose of 10 mg kg-1 intraperitoneally. It is suggested that these three experimental paradigms may be used as models for differentiation of the pharmacological effects of imipramine and desipramine in-vivo.

tofranil medication information

Down-regulation of cortical beta-adrenoceptors is observed in laboratory animals following chronic treatment with many clinically effective antidepressant therapies. [3H]Dihydroalprenolol (DHA) binding to cortical beta-adrenoceptors was examined in mice treated with the functional NMDA antagonists 1-aminocyclopropane-carboxylic acid (ACPC) and MK-801. ACPC and MK-801 reduced [3H]DHA binding by 19 (P less than 0.05) and 21% (P less than 0.05), respectively, while imipramine produced a 23% (P less than 0.05) reduction. No corresponding changes in the KD of [3H]DHA were observed. These findings are consistent with the observation that functional NMDA antagonists are active in animal models commonly used to evaluate antidepressants and may represent a novel approach to the treatment of depression.

tofranil brand name

It is shown that a long experience of defeats in daily zoosocial collisions (ZC) elicits changes in the structure of submissive behaviour. Male mice of C57BL/6J line after 20 defeats demonstrated poses of passive subordination instead of active defence and run away which they manifested in the first ZC. Moreover, new immobile poses appeared which were rare in the first ZC. Submissive animals (CA) demonstrated a decrease of travels in the open field test and an increase of immobility time in the Porsolt test. Chronic administration of imipramine (10 mg/kg, i.p., twice a day during two weeks against the background of repeated ZC) prevented an increase of depressivity, estimated in Porsolt test. Changes were noted in the content of serotonin and 5-HIAA in some brain structures of subordinated mice in comparison to control animals (five days of isolation). The data are discussed from a position of the development of depression in SA of C57BL/6J line as a result of a long nonavoided zoosocial stress.

tofranil 200 mg

This study investigated the involvement of NMDA receptors and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like effects of zinc in the forced swimming test (FST). The immobility times in the FST and in the tail suspension test (TST) were reduced by zinc chloride (ZnCl(2), 30 and 10-30 mg/kg intraperitoneal (i.p.), respectively). The doses active in the FST and TST reduced locomotor activity in an open-field. The antidepressant-like effect of ZnCl(2) in the FST was prevented by pre-treatment of animals with guanosine 5'-monophosphate (GMP), ascorbic acid, L-arginine, or S-nitroso-N-acetyl-penicillamine (SNAP), but not with D-arginine, administered at doses that per se produced no anti-immobility effect. The immobility time of mice treated with ZnCl(2)+MK-801 was not different from the result obtained with ZnCl(2) or MK-801 alone, but ZnCl(2)+imipramine had a greater effect in the FST than administration of either drug alone. Pre-treatment of animals with a sub-threshold dose of ZnCl(2) prevented the anti-immobility effect of MK-801, ketamine, GMP, L-arginine or N(G)-nitro-L-arginine (L-NNA), but did not alter the effect of imipramine or fluoxetine. Taken together, the results demonstrate that zinc produced an antidepressant-like effect that seems to be mediated through its interaction with NMDA receptors and the L-arginine-NO pathway.

tofranil low dose

All randomised trials of desmopressin for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive desmopressin compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were reported. Trials focused solely on daytime wetting were excluded.

tofranil overdose

In addition to supporting traditional claims and previously reported antidepressant properties for POEE, this study shows that POEE prevents stress-induced HPA hyperactivity.

tofranil tablet

Repeated antidepressant treatment attenuates the step-down passive avoidance deficit which is induced by olfactory bulbectomy in rats. Using a shuttlebox passive avoidance procedure, the effects of antidepressants were investigated after various drug withdrawal intervals. Imipramine, amitriptyline, doxepin, bupropion and mianserin were effective at 48 and usually 72 hours after withdrawal, but no significant attenuation of the deficit was seen 4 hours after withdrawal from any antidepressant tested. At least 4 to 7 days of imipramine treatment were required for efficacy. A high dose of d-amphetamine (5 mg/kg) produced similar results while tranylcypromine and haloperidol were inactive at all withdrawal intervals tested. The olfactory bulbectomy syndrome may reflect functional serotonin deficiency, which would be ameliorated through antidepressant-induced alterations in serotonin receptor sensitivity.

tofranil drug classification

A test procedure, inducing a defined state of vigilance in rats, has been investigated to ascertain its usefulness for EEG monitoring of the effects of drugs. In order to prevent spontaneous fluctuations in the level of vigilance, rats were trained to walk in a slowly rotating treadwheel. The level of vigilance recorded under these conditions could be shifted by amphetamine, 1.0 mg/kg p.o., to a higher state of arousal, as shown by a reduction in power in all frequency bands, and by diazepam, 0.3 mg/kg p.o., to a lower state of arousal, as indicated by a rise in the activity at low frequencies. Imipramine (1.0, 3.0 and 10.0 mg/kg p.o.) caused a dose-related reduction in power in the intermediate frequency bands (3-18 Hz).

tofranil online

The effect of joint administration of imipramine (IMI) and magnesium (Mg) on antidepressant-like activity was studied in mice using forced swim test (FST). Mg doses ineffective per se (5 and 10 mg/kg) given jointly with IMI also at ineffective doses (10 and 15 mg/kg) resulted in a potent reduction in the immobility time. Since these combined treatments did not influence locomotor activity, the antidepressant-like activity was not due to non-specific behavioral activation. Moreover, we estimated the effect of joint administration of magnesium and IMI in FST on serum and brain magnesium, IMI and its active metabolite desipramine (DMI) concentrations in mice. Swim stress (mice subjected to FST) increased the magnesium concentration in serum and decreased it in the brain compared to naive animals. Moreover administration of IMI increased (normalized) magnesium brain concentration, without influence on the serum level. Joint administration of IMI and magnesium did not influence magnesium (compared with FST) or IMI and DMI (compared with IMI treatment alone) concentrations in both examined tissues. The present data demonstrated an enhancement of the antidepressant-like effect by joint administration of IMI and magnesium in the FST, and further indicate the particular role of magnesium in the antidepressant action. Since there was no increase in IMI, DMI or magnesium concentration after joint administration of magnesium and IMI, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between magnesium and IMI is accountable for behavioral effect in the FST.

tofranil generic name

The hallmark of agoraphobia is the spontaneous panic attack, a reaction of extreme fearfulness and impending doom with cardiorespiratory symptoms. The end result can be a patient who is housebound. The basic therapeutic principle is confrontation with the avoided object or activity. Controlled clinical experiments demonstrate that both imipramine and phenelzine, the drugs of choice for this prevalent and disabling disorder, have a specific antipanic effect.

tofranil tablet uses

Retrograde ejaculation (RE) is one of the complications of diabetes mellitus. Different therapeutic approaches are present, whether medical or surgical, with limited success rates.

tofranil user reviews

Rat blood exhibited a significant quinone-dependent N-oxide reductase activity towards imipramine N-oxide. The reduction mediated by the blood proceeded in the presence of both NAD(P)H and menadione under anaerobic conditions. When menadione was replaced with 1,4-naphthoquinone or 9,10-phenanthrenequinone, similar results were obtained. The reduction was also mediated by the combination of rat erythrocytes and plasma. The reducing activity was inhibited by dicumarol and carbon monoxide. When boiled plasma was combined with untreated erythrocytes, the N-oxide reducing activity was abolished. In contrast, when boiled erythrocytes were combined with untreated plasma, the activity was unchanged. These results suggest that the activity is caused by the heme of hemoglobin in erythrocytes and quinone reductase in plasma. In fact, erythrocytes and hemoglobin have the ability to reduce the N-oxide when supplemented with DT-diaphorase purified from rat liver in the presence of both NAD(P)H and menadione. Hemoglobin also exhibits N-oxide reductase activity with reduced menadione (menadiol). Furthermore, hematin exhibits a significant reducing activity in the presence of menadiol. The reduction appears to proceed in two steps. The first step is enzymatic reduction of quinones to dihydroquinones by quinone reductase(s) with NADPH or NADH in plasma. The second step is nonenzymatic reduction of imipramine N-oxide to imipramine by the dihydroquinones, catalyzed by the heme group of hemoglobin in erythrocytes. Cyclobenzaprine N-oxide and brucine N-oxide are similarly transformed to the corresponding amines by the above reducing system in blood. These results suggest that blood plays an important role in the reduction of tertiary amine N-oxides to tertiary amines.

tofranil overdose death

Sodium bicarbonate has been recommended for the treatment of arrhythmias induced by tricyclic antidepressants. It is unclear, however, whether this therapy is effective only in the presence of acidosis. A case is presented in which there was an immediate response to sodium bicarbonate in three episodes of ventricular tachycardia despite the presence of alkalosis on two of the three occasions. Given the poor response to conventional therapy of arrhythmias induced by tricyclic antidepressants the use of sodium bicarbonate may be reasonable even in the presence of alkalosis. However, in the presence of pre-existing respiratory or metabolic alkalosis, such therapy is not without risk, and it is suggested that it be reserved for life-threatening situations when the arrhythmia has failed to respond to hyperventilation or antiarrhythmics or both.

tofranil 5 mg

Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues.

tofranil drug

The phosphorylation of substrate proteins by protein kinases plays a key role in signal transduction and function of neurons. Protein kinases have been associated with several physiological and pathological states including depression. The aim of the present study was to investigate the effect of imipramine and electroconvulsive treatment (ECS), both clinically effective treatments of depression, on the activity of calcium/calmodulin dependent protein kinase II (CaM-KII) in the hippocampus. Our results indicate that repeated (but not acute) imipramine and ECS administration significantly decreased CaM-KII activity by 65 and 70%, respectively, in the soluble fractions from hippocampus. This decreased enzyme activity was accompanied by a proportional decrease (60-70%) of the amount of a-CaM-KII in the same fraction. A single and repeated administration of imipramine produced a significant increase in the activity of CaM-KII (50 and 337%, respectively) in the particulate fraction from hippocampus. Similarly, a single and repeated ECS produced an increase in the enzyme activity by 22 and 240%, respectively. The amount of a-CaM-KII in the particulate fraction was not significantly affected by repeated antidepressant administration. It is postulated that changes in CaM-KII activity following chronic antidepressant treatment might represent and important step in expression of its antidepressive action.

Target Point Shipping Method Tracking Delivery Time Price
Worldwide shipping

Worldwide shipping

Registered Mail  Not trackable 14-21 business days USD 20.00 per order
EMS  Trackable, where available 5-9 business days USD 30.00 per order

Delivery time is:

Registered Mail - 14-21 business days, prices - USD 20.00, no signature is required on delivery.
EMS - 5-9 business days, prices - USD 30.00, signature is required on delivery.
Your order will be packed safe and secure and dispatched within 24 hours.

front back side

This is exactly how your parcel will look like (pictures of a real shipping item). It has a look of a regular private letter and does not disclose its contents. Size - 9.4x4.3x0.3 inches (24x11x0.7cm).

 Show Hide 
tofranil buy canada 2017-03-14

Kinetics of electron donor-acceptor (EDA) complex formation of imipramine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was investigated spectrophotometrically in acetonitrile, 1,2-dichloroethane, and chloroform solutions using soft- and hard-modelling approaches. From the results of exploratory analysis of kinetic data and the spectral changes by soft-modelling approaches, evolving factor analysis (EFA) and orthogonal projection approach (OPA), a consecutive two-steps reaction with two intermediates was proposed for the process in acetonitrile and 1,2-dichloroethane media and one with a single intermediate in chloroform solution. Secondly, by applying, multivariate nonlinear least squares hard-modelling approach on the collected experimental kinetic data matrix, the nonlinear parameters (rate constants) as well as the linear parameters (spectral profiles) were obtained by fitting the collected experimental kinetic data matrix to the proposed model. Small values of standard deviation in the resulting parameters and sum of squares of the residuals (ssq) obtained showed the proper selection of the model. Furthermore, the values of lack of fit and percent of explained variance confirmed the correct identified models. Identification of the model with the aid of soft-modelling approaches followed by application of the hard- tofranil buy modelling approaches decreases significantly the rotational ambiguity associated with the obtained concentration and spectral profiles. Variations in the kinetic constants were in complete agreement with the model proposed and the solvent polarities.

tofranil buy canada 2017-03-01

We employed a tofranil buy new form of solid-phase material, the Empore octyl (C8) extraction membrane (SPEM), for the efficient extraction of tricyclic drugs from patients' serum specimens. Both extraction and companion high-performance liquid chromatographic (HPLC) assay of doxepin (DOX), desmethyldoxepin (DDOX), imipramine (IMI), desmethylimipramine (DESI), amitriptyline (AMI), nortriptyline (NOR), clomipramine (CLO), and desmethylchlomipramine (DCLO) are presented here. Routinely, serum (1.0 mL or less) adjusted to pH 5.5 with phosphate buffer is passed through the SPEM secured in a MF-1 microfilter unit. Proteins and potential interferences retained on SPEM are removed with an acetonitrile-water wash. The tricyclic drugs are eluted with HPLC mobile phase and the eluate is injected directly on a Zorbax cyanopropyl (CN) HPLC column, thereby avoiding time consuming evaporation-concentration steps that can affect drug stability. Recovery for all drugs exceeds 90% and analytical responses are linear from a lower limit of sensitivity of 8 micrograms/L up to at least 1000 micrograms/L. Between-run coefficients of variation (CV) range from 2.9 to 8.3% through the concentration range of 75 to 300 micrograms/L. Performance characteristics of the SPEM are compared to those of conventional large particle silica- and polymeric-based sorbents. Within the requirements of this assay, the SPEM extraction requires less sample volume and reduces elution and solvent volumes.

tofranil buy canada 2016-07-15

Maprotiline (Ludiomil) is a dibenzo bicyclooctadiene pharmacologically related to the tricyclic antidepressants and stereochemically having a tetracyclic structure. A controlled, double-blind comparison of maprotiline and imipramine in a group of 71 female outpatients with primary depression is presented. Lasix 40mg Tab Maprotiline was found to be at least as effective as imipramine and significantly better in depressive neurosis. It also showed a bipolar action, being effective in both agitation and retardation.

tofranil buy canada 2016-03-21

We have previously demonstrated that the total glycosides of peony exert antidepressant-like effects in animal models. Paeoniflorin is the main active glycoside of peony. The purpose of this study was to evaluate the antidepressant-like effects of paeoniflorin in a rat model of chronic unpredictable stress (CUS) and its active mechanisms. The results showed that CUS-exposed rats exhibited depressive-like behaviour with reduced weight, low motor activity as well as reduced consumption of sucrose, biochemical changes with increased concentrations of corticosterone and adrenocorticotropic hormone and neurochemical changes with reduced monoamine neurotransmitter levels. Paeoniflorin treatment markedly Asacol 400 Generic increased sucrose consumption and decreased serum corticosterone and adrenocorticotropic hormone levels in the CUS-treated rats. Furthermore, paeoniflorin treatment significantly attenuated CUS-induced reductions in noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid as well as CUS-induced increases in the ratio between the latter two factors. These results suggest that the modulation of the hypothalamic-pituitary-adrenal axis and up-regulation of serotonergic and noradrenergic systems are important mechanisms underlying the antidepressant-like effects of paeoniflorin in CUS-treated rats.

tofranil buy canada 2017-01-20

MDR3 dysfunction is associated with liver diseases. We report here a novel MDR3 activity assay involving in situ biosynthesis in primary hepatocytes of deuterium (d9)-labeled PC and LC-MS/MS determination of transported extracellular PC-d9. Several drugs associated with DILI such as chlorpromazine, imipramine, itraconazole, haloperidol, ketoconazole, sequinavir, clotrimazole, ritonavir, and Benicar 80 Mg troglitazone inhibit MDR3 activity. MDR3 inhibition may play an important role in drug-induced cholestasis and vanishing bile duct syndrome. Several lines of evidence demonstrate that the reported assay is physiologically relevant and can be used to assess the potential of chemical entities and their metabolites to modulate MDR3 activity and/or PC biosynthesis in hepatocytes.

tofranil buy canada 2015-12-22

Antioxidant enzymes and lipid peroxidation in the brain are involved in neuropsychiatric pathologies, including depression. 14- or 28-day chronic stress model induced a depressive syndrome defined by lowered reward sensitivity in C57BL/6J mice and changed gene expression of peroxidation enzymes as shown in microarray assays. We studied how susceptibility or resilience to anhedonia is related to lipid peroxidation in the prefrontal cortex (PFC). With 14-day stress, a comparison of the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) and accumulation of malondialdehyde (MDA) revealed a decrease of the first two measures in susceptible, but not in resilient animals or in stressed mice chronically dosed with imipramine (7mg/kg/day). Acute stress elevated activity of CAT and SOD and dynamics of MDA accumulation in the PFC that was prevented by imipramine (30mg/kg). 28-day stress evoked anhedonia lasting two but not five weeks while behavioural invigoration was detected at the latter time point Zithromax Pediatric Dosing in anhedonic but not non-anhedonic mice; enhanced aggressive traits were observed in both groups. After two weeks of a stress-free period, CAT and SOD activity levels in the PFC were reduced in anhedonic animals; after five weeks, only CAT was diminished. Thus, in the present chronic stress depression paradigm, lasting alterations in brain peroxidation occur not only during anhedonia but also in the recovery period and are accompanied by behavioural abnormalities in mice. This mimics behavioural and neurochemical deficits observed in depressed patients during remission which could be used to develop remedies preventing their relapse.

tofranil buy canada 2016-04-09

Tricyclic antidepressants (TCAs) Strattera Therapeutic Dose have been used to treat melancholic depression, which has been associated with elevated hypothalamic-pituitary-adrenocortical (HPA) axis activity, whereas patients suffering from atypical depression, which is often associated with decreased HPA axis activity, show preferential responsiveness to monoamine oxidase inhibitors (MAOIs). We previously reported drug-specific effects of the TCA imipramine and the MAOI phenelzine on HPA axis-relevant endpoints in mice that may explain differential antidepressant responses in melancholic vs. atypical depression. However, selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in both melancholic and atypical depression. We therefore hypothesized that SSRIs would share HPA axis-related effects with either TCAs or MAOIs. To test this hypothesis, we measured HPA axis-relevant gene expression in male C57BL/6 mice treated for 5 weeks with 10 mg/kg/day fluoxetine. To control for potential fluoxetine-induced changes in glucocorticoid secretion, mice were adrenalectomized and given fixed levels of glucocorticoids. Fluoxetine decreased glucocorticoid receptor (GR) gene expression in the prefrontal cortex, amygdala, locus coeruleus and dorsal raphé nucleus, and increased locus coeruleus tyrosine hydroxylase and dorsal raphé nucleus tryptophan hydroxylase-2 (TPH2) gene expression. These results resembled those that we previously reported for MAOI treatment, but included decreases in GR and increases in TPH2 gene expression in the dorsal raphé nucleus that were induced by TCAs but not MAOIs. Correlating with inhibitory effects on central amygdala GR gene expression, fluoxetine also decreased amygdala corticotropin-releasing hormone gene expression, an effect not previously observed with MAOIs or TCAs. These actions may be relevant to the efficacy of SSRIs in treating a range of depression and anxiety disorders.

tofranil buy canada 2015-09-10

A monoclonal antibody was used to study the dose-response relationship for antibody-mediated redistribution of tricyclic antidepressants (TCA) in rats. The antibody (anti-TCA) was an IgG1 with Ka = 3.0 x 10(8) M-1 for desipramine (DMI) and 2.2 x 10(8) M-1 for imipramine (IMI). Anesthetized rats received 1 mg DMI (10% of the toxic dose), followed in 15 min by anti-TCA iv at doses representing anti-TCA/DMI molar ratios of 0.003, 0.013, and 0.07. Anti-TCA produced prompt, dose-related increases in the serum DMI concentration of 33, 164, and 776%. Similar results were obtained in rats treated with IMI. The highest dose of anti Zocor 10mg Medication -TCA reduced the concentration of IMI in the heart. In a second protocol, the anti-TCA dose was kept constant and the DMI or IMI dose varied. The increase in serum drug concentration was 1750, 1260, and 150% (DMI) and 1460, 1200, and 170% (IMI) at drug doses of 0.1, 10, and 1000 micrograms. Thus, the percentage increase in serum drug concentration was diminished only 12-fold (DMI) or 9-fold (IMI) by a 10,000-fold increase in drug dose. At the highest anti-TCA/DMI ratio (lowest DMI dose), tissue DMI concentrations were significantly reduced. We conclude that 1) anti-TCA can effect substantial redistribution of a subtoxic dose of DMI or IMI, even when the antibody dose is less than equimolar to the TCA dose, and 2) the extent of TCA redistribution depends upon the doses of both antibody and drug; anti-TCA is most effective when the body burden of TCA is high. These data support the potential therapeutic use of anti-TCA for DMI or IMI toxicity, and should be useful in anticipating the dose and affinity of anti-TCA required.

tofranil buy canada 2016-11-25

There was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone. There was limited evidence to suggest that desmopressin, imipramine and enuresis alarms therapy were better than the included drugs to which they were compared. In other reviews, desmopressin, tricyclics and alarm interventions have been shown to be effective during treatment. There was also evidence to suggest that combination therapy with anticholinergic therapy increased the Priligy Buy Uk efficacy of other established therapies such as imipramine, desmopressin and enuresis alarms by reducing the relapse rates, by about 20%, although it was not possible to identify the characteristics of children who would benefit from combination therapy. Future studies should evaluate the role of combination therapy against established treatments in rigorous and adequately powered trials.

tofranil buy canada 2016-01-14

The pro-inflammatory tigliane esters 12-deoxyphorbolphenylacetate (12-DOPPA) and 12-deoxyphorbolphenylacetate-20-acetate (12-DOPPAA) at a dose of 0.1 microgram induced erythema in the mouse ear. Observations of ear redness were made both two and four hours after application. Indomethacin was only partly successful as an antagonist since 10% inhibition of 12-DOPPA and no inhibition of 12-DOPPAA induced erythema was produced four hours after application. The free radical scavengers, phenol, thioanisole and sodium benzoate all produced less than 30% inhibition of 12-DOPPA induced erythema and less than 15% inhibition of 12-DOPPAA, whereas aminopyrine produced 70% and 25% inhibition of 12-DOPPA and 12-DOPPAA respectively. The fact that free radical scavengers (with the exception of aminopyrine) and indomethacin, failed to markedly change the mouse ear reaction to 12-deoxyphorbol esters, indicated that this erythema is not entirely mediated via cyclooxygenase products. Mepyramine and cyproheptadine also failed to inhibit the erythema, whereas hydrocortisone produced a 55% inhibition of the 12-DOPPA and a 20% inhibition of the 12-DOPPAA reaction. The membrane stabilising agents trifluoperazine, promethazine, imipramine and desmethylimipramine were the most Altace Pill Identification successful compounds used in inhibiting both 12-DOPPA and 12-DOPPAA induced erythema. In addition propranolol, which inhibits stimulus activation of phospholipase A2, produced 70% and 55% inhibition of the reaction of mice ears to 12-DOPPA and 12-DOPPAA.

tofranil buy canada 2017-05-01

This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear Lasix Medicine relevance to patients and clinicians were not reported in any of the included studies.

tofranil buy canada 2016-08-14

Slices of rabbit lung tissue (approximately 150 mg; 0.5 mm) were incubated in 5 ml of Krebs-Ringer phosphate buffer, in the presence of 0.25 mM [14C]chlorphentermine (CP) with shaking at 37 degrees C and under an atmosphere of an O2/CO2 mixture (95 : 5). Incubation medium (M) and tissue (T) were analyzed for radioactivity. Uptake of CP reached a plateau after 30 min at a T/M ratio of 20. Upon varying the concentration of [14C]CP from 0.125 mM to 2 mM, the concentration-response curve was seen to saturate and the T/M ratio decreased with increasing concentration. Substituting LiCl for NaCl or increasing the K+ content in the medium decreased CP uptake. Incubation of slices with Na+-pump inhibitors, harmaline and iodoacetate, significantly decreased CP uptake. Chloroamphetamine, desimipramine, imipramine, morphine, chlorpromazine, dieldrin, methadone, amphetamine (each at 1 mM) and incubation at 10 degrees C inhibited CP uptake. Imipramine and amphetamine were both effective in displacing previously accumulated CP from the tissue slices. Efflux of CP from the lung slices was biphasic and was not affected by removal of Na+ from the medium. Binding of CP to lung homogenate was unaffected by substituting LiCl for NaCl or by the presence of 1 mM iodoacetate. However, 1 mM harmaline or 1 mM imipramine decreased CP binding. These studies offer evidence for a partially Na+-dependent, active uptake process for pulmonary sequestration of CP compatible with earlier findings obtained with perfused intact lung preparations.

tofranil buy canada 2016-04-04

The effects of single oral doses of binedaline (100 mg), imipramine (50 mg) and placebo administered without and with alcohol (0.8 g/kg) were compared on performance tasks (posturographic recordings, i.e., body sway to study alertness, squares test to explore attention and concentration) and subjective assessments in 12 healthy volunteers. The tasks were completed 1.4 and 8 h after drug administration. Blood samples were collected at the same times. Binedaline had no significant effects on any of the task parameters and did not interact with alcohol. Imipramine alone impaired performance at 4 h as shown on posturographic parameters. These disturbances were potentiated by the intake of alcohol. No pharmacokinetic interaction was noted.

tofranil buy canada 2016-07-08

The application of various techniques for the analysis of equivalence data suggests that trazodone and imipramine are of approximately equivalent efficacy. The data are compatible with small differences in efficacy, but the differences are of a magnitude such that they are unlikely to be of clinical significance.

tofranil buy canada 2016-12-11

It has been argued that a mechanism of clomipramine's efficacy for obsessive-compulsive disorder is its reduction of excessive autonomic reactivity. The present study evaluated this proposed mechanism of action by assessing the effect on autonomic responding of imipramine, which is structurally similar to clomipramine, but lacks therapeutic efficacy for obsessive-compulsives. Twenty-three obsessive-compulsive patients received three sessions of 20 unsignalled 1000-Hz, 100-dB tones of 1-sec duration and 100-msec rise-time. Skin conductance level, response frequency and magnitude, and heart rate were scored for an adaptation period and for each tone onset. Six weeks after the first tone session, during which half of the subjects received imipramine while the remainder received placebo, the second tone assessment was performed. A third tone assessment was performed after an additional 4 weeks of medication. Percentage of nonresponders was also evaluated for each group. Imipramine reduced electrodermal activity and increased heart rate. Skin conductance level and both number and amplitude of responses decreased significantly after 6 weeks of imipramine, compared with placebo, with further attenuation of electrodermal activity after 10 weeks of the drug. Electrodermal nonresponding increased dramatically for the imipramine group as compared to the nondrug group. These results reveal effects of imipramine on autonomic responding, and cast doubt on the hypothesis that a mechanism for successful drug treatment of obsessive-compulsive disorder is decreased autonomic reactivity.

tofranil buy canada 2016-09-21

To evaluate the behavioral effect of pyridoxine on the antidepressant action of imipramine.

tofranil buy canada 2017-06-08

Microelectrode techniques were used to study the electrophysiologic effects of the tricyclic antidepressant (TCA) drugs imipramine , amitriptyline, doxepin, desipramine, protriptyline, and nortriptyline on isolated Tyrode's ([K +]o= 4.0 mM) superfused dog Purkinje fibers. Drug concentrations ranged from 10(-7) to 10(-5) M. TCA drug concentrations greater than 10(-6) M resulted in decreases in action potential amplitude, duration, and maximum slope of phase O (Vmax). Simultaneously with decreases in action potential duration, the effective refractory period decreased. In addition, the voltage time course of repolarization between proximally and distally recorded action potentials became less obvious. Imipramine, doxepin, protriptyline, and nortriptyline (10(-6), 10(-5) M) depressed membrane responsiveness. Superfusion of dog Purkinje fibers with 10(-5) M concentrations of TCA drugs resulted in conduction delay, postrepolarization refractoriness and, occasionally, total inexcitability. TCA drugs caused an increase in escape time and a decrease in spontaneous rate of spontaneously automatic Purkinje fibers equilibrated with epinephrine (10(-7) M) in 5 X 10(-5) M EDTA. Imipramine, doxepin, protriptyline, and nortriptyline abolished extra nondriven action potentials, and diminished oscillatory afterpotentials in dog Purkinje fibers exposed to toxic concentrations of ouabain (2 X 10(-7) M).

tofranil buy canada 2016-04-19

Fluoxetine, a selective 5-HT uptake inhibitor, inhibited 15 mM K(+)-induced [3H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations greater than 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K+ used to depolarize the synaptosomes and the concentration of external Ca2+. Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [3H]5-HT release induced by the Ca(2+)-ionophore A 23187 or Ca(2+)-independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K(+)-induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca2+ channels and Ca2+ entry. Whereas fluoxetine and paroxetine inhibited binding of [3H]nitrendipine to the dihydropyridine-sensitive L-type Ca2+ channel, the less selective uptake inhibitors did not alter binding. The dihydropyridine antagonist nimodipine partially blocked fluoxetine-induced inhibition of release. Moreover enhanced K(+)-stimulated release due to the dihydropyridine agonist Bay K 8644 was reversed by fluoxetine. Fluoxetine also inhibited the K(+)-induced increase in intracellular free Ca2+ in fura-2 loaded synaptosomes. These data are consistent with the suggestion that fluoxetine inhibits K(+)-induced [3H]5-HT release by antagonizing voltage-dependent Ca2+ entry into nerve terminals.

tofranil buy canada 2016-05-26

The aim of this research was to find out whether increased plasma cortisol levels appear in unipolar or bipolar patients with major depressive disorder (MDD) and whether the effective antidepressant treatment by imipramine and fluoxetine leads to regulation of the cortisol level. Cortisol levels were studied in two groups of patients with major depressive disorder: unipolar and bipolar patients treated with fluoxetine (doses: 20-60 mg/day). This group included 5 patients (age 29-46 yr); unipolar and bipolar subjects treated with imipramine (50-150 mg/day), this group included 5 patients (aged 24-70 yr). Cortisol and fluoxetine or imipramine plasma levels were assessed using HPLC methods: before treatment, after 3, 6 and 24 h of drug administration as well as in the 2nd, 4th, 6th, and 8th week of antidepressant treatment. HPLC methods were previously validated. The research conducted and the clinical data may be useful for proving the essential role of enhanced HPA axis activity for the pathogenesis and depressive disorder proceedings.

tofranil buy canada 2016-12-25

In patients with proton-pump inhibitor (PPI) resistant reflux symptoms, ambulatory 24 h pH impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Using this technique it has been suggested that patients with typical reflux symptoms and a normal upper endoscopy should be subclassified as follows: normal endoscopy and abnormal distal acid esophageal exposure (patients with acid reflux); normal endoscopy, with normal distal acid esophageal exposure and a positive symptom association for either acid or nonacid reflux (patients with hypersensitive esophagus); and normal endoscopy, normal distal acid esophageal exposure and a negative symptom association for acid and nonacid reflux (patients with functional heartburn). Although for patients with a normal endoscopy and abnormal distal acid esophageal exposure more aggressive acid suppression can be recommended, managing patients with hypersensitive esophagus and functional heartburn remains a real challenge.Therefore, investigators have evaluated the role of tricyclic antidepressants or selective-serotonin reuptake inhibitors (SSRIs) in influencing esophageal perception. Imipramine has been shown to decrease pain perception in healthy male volunteers and improve symptoms of patients with chest pain and normal coronary angiograms. Trazodone improved symptoms in patients with esophageal contraction abnormalities, while administration of SSRIs lowered chemical and mechanical sensitivity and benefited patients with diffuse esophageal spasm. Furthermore, in a recent study conducted by our group, citalopram administered once daily for 6 months was effective in a select group of patients with hypersensitive esophagus, suggesting that there is a role for SSRIs in the treatment of this disorder.

tofranil buy canada 2015-03-19

The polygraphically recorded sleep-wake continuum of 21 Prader-Willi syndrome (PWS) patients was compared with that of 19 normal people. In the Prader-Willi group, excessive daytime sleepiness (EDS) is found in 95% of subjects, and rapid eye movement (REM) sleep disorders occur in 52%. These two features were significantly different from the normal group of subjects. No indications were found for the presence of the apnoea syndrome. The REM sleep disorders are: sleep onset rapid eye movements (SOREM), REM sleep in naps, many arousals during REM sleep, and a significant decrease in total REM sleep. These disturbances in the Prader-Willi group, combined with the presence of EDS and sometimes of cataplexy, are likely to be expressions of a narcoleptic syndrome although this was not sustained by the HLA-DR2 expression above normal. The quality of life of PWS subjects can be improved in some cases by treating them as narcoleptic patients.

tofranil buy canada 2015-05-03

We have investigated the process of catecholamine uptake in guinea-pig chromaffin cells. Isolated guinea-pig chromaffin cells accumulate [3H]norepinephrine and [3H]epinephrine by a saturable transport system. Catecholamine uptake is dependent upon temperature, energy, and extracellular Na+. The apparent KmS for norepinephrine and epinephrine transport are approximately 1 and 3.5 microM, respectively; the transport maximum (Vmax) for both compounds is about 100 pmol/min/mg protein. The uptake of norepinephrine into chromaffin cells is inhibited by imipramine (Ki = 50 nM) and by desmethylimipramine (IC50 = 20 nM). In both its substrate specificity and its sensitivity to pharmacological inhibition, the catecholamine uptake system in chromaffin cells is similar to the catecholamine transport system previously described in sympathetic neurons. Decreasing external Na+ from 130 to 19 mM increases the apparent Km for norepinephrine to 2.8 microM. Decreasing external norepinephrine increases the Na+ concentration required for half-maximal transport. Agents that depolarize chromaffin cells, such as acetylcholine and veratridine, significantly inhibit [3H]norepinephrine uptake. This decrease in uptake is due to an increase in the apparent Km for norepinephrine. The inhibition of [3H]norepinephrine uptake by depolarizing agents cannot be accounted for by the preferential release of newly-accumulated [3H]norepinephrine, or by the competitive inhibition of [3H]norepinephrine uptake by secreted catecholamines. The inhibition of catecholamine uptake by depolarizing agents suggests that the transport system may be regulated by the membrane potential. Norepinephrine and epinephrine that are spontaneously released from the adrenal medulla may be recaptured in vivo. The inhibition of transport by acetylcholine may prevent the re-uptake of catecholamine released during the physiological stimulation of secretion.

tofranil buy canada 2015-01-24

Paroxetine demonstrated a cost-benefit relative to imipramine when the continuation rate was > or = 47%. Clinical trials of paroxetine have reported continuation rates of 41% to 65%, suggesting that paroxetine is a cost-effective alternative to imipramine in the 1-year management of patients with moderate to severe depression.

tofranil buy canada 2017-12-02

Centrally active drugs of the phenothiazine-, butyrophenone- and iminodibenzyl class markedly decreased the rate of dopamine oxidation in the presence of rat brain catecholamine oxidase.

tofranil buy canada 2017-02-10

Chronic administration of imipramine with drinking water to Wistar rats for two months did not affect the [3H]dihydroalprenolol binding to lymphocytic membranes, though the treatment depressed the radioligand binding to cerebral cortical membranes. The result suggests that the beta-adrenoceptor downregulation caused by the antidepressant in the central nervous system is not reflected in the lymphocytes.

tofranil buy canada 2017-12-17

Clocapramine was introduced into clinical use as a successor to carpipramine which is designated as a "désinhibiteur' by Deniker et al. Pharmacological and biochemical studies were carried out in order to elucidate the central action of clocapramine. Antidopaminergic activity of clocapramine was more potent than that of carpipramine. Clocapramine did not show any imipramine-like action; on the other hand, carpipramine partially did. We discuss the correlation between the preclinical findings so far obtained and clinical disinhibitory activity.

tofranil buy canada 2016-07-10

The investigated antidepressant drugs added to control liver microsomes produced certain inhibitory effects on CYP2C11 activity, which were moderate (sertraline, nefazodone and clomipramine: Ki = 39, 56 and 66 μM, respectively), modest (fluoxetine and amitriptyline: Ki = 98 and 108 μM, respectively) or weak (imipramine and desipramine: Ki = 191 and 212 μM, respectively). Mirtazapine had no inhibitory effect on CYP2C11 activity. One-day exposure of rats to the antidepressant drugs did not significantly change the activity of CYP2C11 in liver microsomes; however, imipramine, desipramine and fluoxetine showed a tendency to diminish the activity of CYP2C11. Of the antidepressants studied, only desipramine and fluoxetine administered chronically elevated CYP2C11 activity; those effects were positively correlated with the observed increases in the enzyme protein level.

tofranil buy canada 2016-09-15

The antidepressant effect exhibited by Marsilea minuta extract may be due to its effect on 5-HT2A density in rat frontal cortex.

tofranil buy canada 2015-05-03

The goal of this study was to evaluate the plausibility and accuracy of commercially available on-site immunoassay urinalysis kits for the screening of compounds of interest within food matrices. In conjunction with this study, a sensitive, robust, and reproducible analytical method, utilizing solid-phase extraction liquid chromatography/quadrupole ion trap/time-of-flight mass spectrometry for confirmation analysis, was developed. The food matrices analyzed were tomato juice, apple juice, milk, beer, white wine, ground beef, powdered milk, and all-purpose flour. Compounds fortified into the food matrices included heroin, phencyclidine, cocaine, benzoylecgonine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, imipramine, doxepin, nitrazepam, diazepam, oxazepam, temazepam, alprazolam, flunitrazepam, clonazepam, and lorazepam. Standard curves were prepared for each matrix from 10 to 500 ng/ml for each analyzed compound. All liquid chromatography/tandem mass spectrometry samples were fortified with 20 microl of deuterated internal standard at 90 ng/ml. Quality control standards were prepared at 20 and 400 ng/ml, and > 90% were within 2 SD of the mean for each analyte. The test kits were found to produce up to 85% of the expected results based on concentration levels of adulterants (i-Screen in milk). This study shows that lateral-flow immunoassay test kits are plausible as a rapid, accurate, and reliable screening method in the event of adulteration of the food supply.

tofranil buy canada 2016-09-28

In an effort to explore possible changes in 5-hydroxytryptamine (5-HT) metabolism in idiopathic torsion dystonia (ITD), platelets from patients were studied. Platelet 5-HT concentrations did not differ from those in matched controls. 5-HT uptake by the platelets was also studied, and the results demonstrated significantly higher Km values, but Vmax values were normal among patients. Inhibition by imipramine of 5-HT uptake by platelets taken from ITD patients was also normal. The therapeutic implications of the low affinity of 5-HT to its platelet receptors are discussed.

tofranil buy canada 2017-03-30

This study extends previous findings from our group using the SSRI citalopram as an antidepressant. Imipramine and citalopram induce similar changes in the endocrine response to buspirone in depressed patients. As the direction of change in ACTH-cortisol and PRL responses after treatment is the opposite, we cannot substantiate increases or decreases in the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus by long-term imipramine treatment and/or resolution of illness. Therefore, the hormonal changes may result from different or multiples unknown mechanisms.

tofranil buy canada 2017-08-08

Alprazolam is the first of the triazolobenzodiazepines to be studied in a large population of depressed patients. In a six-week, double-blind multicenter comparison of alprazolam, imipramine hydrochloride, and placebo in the treatment of 723 patients with depression, the two active drugs were statistically more effective than placebo. Alprazolam was at least as effective as imipramine in relieving depressive symptoms, significantly more effective in relieving somatic symptoms, and showed an earlier onset of activity in some measurements. Anticholinergic side effects were reported most often by patients receiving imipramine, while drowsiness was the only side effect reported most often in the alprazolam group. The Feighner Diagnostic Criteria and prestudy and poststudy intercenter conferences with videotaped patient interviews ensured interrater reliability.

tofranil buy canada 2015-08-30

Stewart et al (2009) have outlined the evidence in support of the validity of the DSM-IV definition of the 'With Atypical Features' episode specifier. Although recognizing the historical significance and clinical utility of the concept of atypical depression, this article takes issue with the DSM-IV criteria. It is concluded that mood reactivity, the A or obligative criterion, is neither significantly associated with the other symptomatic criteria nor useful to diagnose atypical depression, and thus should be eliminated. Problems with operationalization, specification, and reliability of ratings of the diagnostic criteria further limit validity. Despite these limitations in classification, many of the features associated with atypical depression are linked to an early onset of affective illness, including trait-like interpersonal sensitivity, comorbid social anxiety and agoraphobia, a history of childhood physical or sexual trauma, and indicators of the 'soft' side of the bipolar spectrum. Neurophysiologic studies also suggest that chronic, early-onset atypical depressions differ from both melancholia and normality. Re-analyses of the Columbia group's seminal studies suggest that preferential response to phenelzine vs imipramine--arguably the strongest validator of atypical depression--similarly appears to be limited to patients with chronic, early-onset syndromes. The criteria for atypical depression need to be revised in DSM-V, including sharpening the operational definitions for the specific symptoms. The importance of age of onset and comorbid anxiety warrant further study. Research examining the validity of a subform of atypical depression characterized by trait-like interpersonal sensitivity and a chronic, early-onset course may further enhance the clinical utility of the DSM-V classification.

tofranil buy canada 2017-05-11

We found 74 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

tofranil buy canada 2017-02-16

The Michaelis constant (KM) for cytochrome P450-mediated drug biotransformation reactions can be an important parameter in understanding the potential for a drug to exhibit saturable metabolism in vivo and nonlinear dose-exposure relationships. KM values were measured for several drug biotransformation reactions using recombinant heterologously expressed human enzymes. These determinations were made using an approach of monitoring substrate loss ("in vitro t1/2" method) at multiple substrate concentrations, with the objective of comparing KM values determined by this approach with KM values determined using the conventional approach of measuring product formation rates at several substrate concentrations. The reactions examined were CYP2C9-catalyzed diclofenac 4'-hydroxylation, CYP2D6-catalyzed dextromethorphan O-demethylation and thioridazine S-oxidation, CYP2C19-catalyzed imipramine N-demethylation, CYP3A4-catalyzed midazolam 1'-hydroxylation, and CYP1A2-catalyzed tacrine 1-hydroxylation. KM values spanned an 80-fold range from 0.12 microM (CYP2D6-catalyzed thioridazine S-oxidation) to 9.8 microM (CYP2C19-catalyzed imipramine N-demethylation). On average, KM values determined by the substrate depletion approach were within 1.54-fold of those determined by measuring product formation. Thus, KM values can be determined for drug metabolism reactions without requiring knowledge of metabolite structures or requiring authentic standards of metabolites for use in construction of standard curves for quantitative bioanalysis. The in vitro t1/2 approach of determining KM values should be useful in early drug discovery efforts to identify those compounds with low KM values and, hence, a greater probability of exhibiting supraproportional dose-exposure relationships.

tofranil buy canada 2016-04-13

The possible clinical significance of the plasma protein binding of tricyclic antidepressants has been evaluated using imipramine (IMI), a typical tricyclic. Using equilibrium dialysis, the in vitro binding of IMI to plasma was compared to that of brain tissue. Cerebrospinal fluid (CSF) IMI was used as an independent measure of 'free' drug in the central nervous system. Intrinsic metabolic clearances were calculated on the basis of steady-state plasma IMI concentrations. There were three significant results: (1) variations in plasma binding are not great; (2) plasma protein binding does not limit the entry of IMI into the CSF; (3) variations in metabolism (intrinsic clearance) account for almost all variations in CSF concentrations of drug. It is concluded that measurement of free tricyclic antidepressant is not indicated in studies of clinical efficacy.

tofranil buy canada 2016-06-21

Oxidative stress disturbances have been reported in depressed patients and in animals submitted to stress. Recent evidence suggests that antidepressants may have antioxidant properties. However, the therapeutic potential of antioxidants as antidepressant drugs has not been systematically investigated. Therefore, this study tested the hypothesis that N-acetyl-L-cysteine (NAC), a cysteine prodrug with powerful antioxidant activity, would possess antidepressant-like properties in the forced swimming test. Male Wistar rats were subjected to 15 min of forced swimming and immediately afterward, 5, and 23 h later received intraperitoneal injections of NAC (5, 15, 50, 150, and 250 mg/kg), imipramine, (15 mg/kg) or vehicle. One hour later they were submitted to the 5 min test swimming session, where immobility time was recorded. Independent groups of animals received the same treatments and their exploratory activity was measured in an open arena for 5 min. NAC (at the doses of 15, 50, and 150 mg/kg) and imipramine induced a significant decrease in immobility time without changing exploratory behavior measured in an open arena. These results suggest that antioxidants such as NAC may have antidepressant effects.

tofranil buy canada 2017-04-24

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders.