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PubMed2006

Prevalence of contraindicated medical conditions and use of precluded medications in patients with painful neuropathic disorders prescribed amitriptyline.

Amitriptyline is a tricyclic antidepressant that is historically indicated and used to manage depression. More recently, due to clinical evidence demonstrating efficacy, it is often prescribed in the management of painful neuropathic disorders (PNDs). However, the amitriptyline label contains numerous preclusions (contraindications, warnings/precautions, drug interactions). Our objective was to measure the frequency of amitriptyline prescriptions in PND patients using the U.K. General Practice Research Database and assess whether any prescriptions were given to patients with preclusions listed in the product label. We identified a total of 13,546 patients (mean age 59 +/- 16.2 years; 66.7% female) who had a diagnosis of a PND and received > or =1 prescription for amitriptyline between July 1998 and June 2001. Nearly half (46.7%) of PND patients prescribed amitriptyline had > or =1 preclusion for its use; 3.5% had > or =1 contraindication; 22% had > or =1 warning/precaution; and 33% received > or =1 medication with a potential for drug interactions with amitriptyline. Preclusions were more likely in women than in men (48.3% vs. 43.4%, P < 0.0001); their incidence increased with age (42.8%, 50.4%, 55.1%, and 52.3% among those ages <65, 65-74, 75-84, and 85+ years, P < 0.0001), and the number of patients with preclusions was the highest in the phantom limb pain group (67.4%) and lowest in the atypical facial pain group (42.9%), P < 0.001. The average daily amitriptyline doses (starting: 33.6 +/- 32.4 mg; maintenance: 42.1 +/- 39.9 mg) were low compared to those used for the treatment of depression. Results indicate that, in a significant number of cases, the existence of preclusions did not prevent the prescribing of amitriptyline. Our findings raise a potential concern about the way this medication is being used. However, the clinical significance of these data is, as yet, unclear. Although, in theory, adverse outcomes may have been associated with this practice, we could not confirm this with this database analysis.

Adolescent↗
PubMed1987

Formation of a quaternary N-glucuronide of amitriptyline in human liver microsomes.

Amitriptyline N-glucuronide was isolated from urine of a patient treated with therapeutic doses of amitriptyline. The glucuronide was hydrolyzed by hot alkaline treatment and, to a lesser degree, by treatment with beta-glucuronidase. A method for the direct measurement of amitriptyline glucuronide by HPLC was developed. Human liver microsomes were shown to glucuronidate amitriptyline in the presence of UDPGA, and the activity varied 7-fold among microsomes from 13 different human livers. The glucuronidation of amitriptyline was inhibited by p-nitrophenol but not by morphine. E-10-hydroxynortriptyline, a major metabolite of amitriptyline, had only a slight inhibitory effect on the glucuronidation of amitriptyline. No significant correlation was found between the glucuronidation of amitriptyline and that of E-10-hydroxynortriptyline in the microsomes studied.

Amitriptyline↗
PubMed1985

Frequency-dependent effects of amitriptyline on ventricular conduction and cardiac rhythm in dogs.

Although overdoses of tricyclic antidepressant are known to produce both sinus tachycardia and ventricular tachyarrhythmias in man, these have been assumed to occur by independent mechanisms. This study was designed to evaluate the relationship of ventricular activation frequency to the cardiotoxic effects of amitriptyline. When amitriptyline was infused into dogs with formalin-induced atrioventricular (AV) block to evaluate a broad range of pacing frequencies, the drug produced dose-related QRS prolongation that was markedly frequency dependent. Similar frequency-dependent depression of the maximum rate of depolarization (Vmax) was noted for canine Purkinje fibers superfused with amitriptyline in vitro. The time constant of recovery from amitriptyline-induced block was dose independent and averaged 228 msec in vivo and 216 msec in vitro. When amitriptyline was infused into dogs with intact AV conduction, sinus tachycardia occurred within 15 min, followed by progressive QRS prolongation and ventricular tachyarrhythmias after an average 29 min. Slowing of sinus rate by vagal stimulation (seven dogs) or intravenous metoprolol (five dogs) reproducibly reversed the QRS prolongation and ventricular tachyarrhythmias caused by amitriptyline. These studies show that amitriptyline produces frequency-related depression of ventricular conduction in vivo, with a time dependence similar to effects on the maximum rate of depolarization in vitro. Interventions that slow heart rate reverse the adverse effects of amitriptyline on ventricular conduction and cardiac rhythm.

Action Potentials↗
PubMed2001

Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials.

BACKGROUND: Tricyclic antidepressants have similar efficacy and slightly lower tolerability than selective serotonin reuptake inhibitors (SSRIs). However, there are no systematic reviews assessing amitriptyline, the reference tricyclic drug, v. other tricyclics and SSRIs directly. AIMS: To review the tolerability and efficacy of amitriptyline in the management of depression. METHOD: A systematic review of randomised controlled trials (RCTs) comparing amitriptyline with other tricyclics/heterocyclics or with an SSRI. RESULTS: We reviewed 186 RCTs. The overall estimate of the efficacy of amitriptyline revealed a standardised mean difference of 0.147 (95% CI 0.05-0.243), significantly favouring amitriptyline. The overall OR for dropping out was 0.99 (95% CI 0.91-1.08) and that for side-effects was 0.62 (95% CI 0.54-0.70), favouring the control drugs. With drop-outs included as treatment failures, the estimate of the effectiveness of amitriptyline v. tricyclics/heterocyclics and SSRIs showed a 2.5% difference in the proportion of responders in favour of amitriptyline (number needed to treat 40, CI 21-694; OR 1.12 (95% CI 1.01-1.24)). CONCLUSIONS: Amitriptyline is less well tolerated than tricyclics/heterocyclics and SSRIs, but slightly more patients treated on it recover than on alternative antidepressants.

Amitriptyline↗
PubMed2006

The neurotoxic effects of amitriptyline are mediated by apoptosis and are effectively blocked by inhibition of caspase activity.

Oral tricyclic antidepressants, widely used as adjuncts in the treatment of chronic pain, block sodium channels in vitro and nerve conduction in vivo. However, toxicity of amitriptyline has been observed after neural application. We therefore investigated the mechanism and possible prevention of amitriptyline neurotoxicity. To assess dose-dependent neurotoxicity of amitriptyline, we incubated neuron cultures from adult rat dorsal root ganglia with amitriptyline and quantified neuronal survival. Additionally, we investigated accepted markers of apoptosis (mitochondrial membrane potential, cytosolic cytochrome c, and activated caspase-3) and co-incubated amitriptyline with an inhibitor of caspase activity, z-vad-fmk, to assess the effect on cell survival. We found a dose-dependent neurotoxic effect of amitriptyline. Neurons incubated with amitriptyline exhibited loss of mitochondrial membrane potential, release of cytochrome c into the cytoplasm, and activation of caspase-3. Co-incubation with z-vad-fmk substantially improved neuronal survival in culture. In conclusion, amitriptyline-induced neurotoxicity is mediated by apoptosis and is attenuated by inhibition of caspase activity, suggesting that inhibition of apoptotic pathways may be efficient at alleviating local anesthetic-induced neurotoxicity. In vivo studies will have to corroborate whether the co-injection of anti-apoptotic drugs with local anesthetics decreases neurotoxic side effects.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Amitriptyline-induced constipation in cynomolgus monkeys is beneficial for the evaluation of laxative efficacy.

In an attempt to create an animal model of constipation in monkeys, amitriptyline was administered to cynomolgus monkeys at doses of 10-160 mg/kg body weight via a nasogastric tube. Normal control monkeys excreted feces frequently throughout the day. Monkeys treated with amitriptyline at doses of 10-40 mg/kg showed delays in feces excretion. The 60 mg/kg treated monkeys for the most part did not excrete feces during the 24 h after amitriptyline administration. The 80 and 120 mg/kg treated monkeys did not excrete feces until 24 h from administration of amitriptyline, and also showed prolonged crouching and lethargy. On the other hand, 160 mg/kg treated monkeys died within 24 h after administration. We therefore felt that the optimal dose for creating constipation in the monkeys was 60 mg/kg. We tested the appropriateness of this amitriptyline-induced constipated monkey model by observing the effects of a new laxative, the herbal medicine ND-10 and the commercially available laxative bisacodyl. Control monkeys (those not receiving ND-10 or bisacodyl) treated with 60 mg/kg amitriptyline did not excrete feces up to 32 h after amitriptyline administration in 2 of 3 monkeys. However, all monkeys treated with one tablet of ND-10 excreted feces. Also, in 4 monkeys administrated with bisacodyl, 3 excreted feces. In this study, we confirmed that constipation can be caused in cynomolgus monkeys by oral administration of amitriptyline. This model may also be useful for the evaluation of laxatives.

Amitriptyline↗
PubMed2000

Syncope associated with concurrent amitriptyline and fluconazole therapy.

OBJECTIVE: To report on a 12-year-old white male with prostatic rhabdomyosarcoma who experienced episodes of syncope attributed to concurrent amitriptyline and fluconazole therapy, confirmed by readministration. CASE REPORT: The patient began experiencing syncopal episodes periodically over a seven-month period. These repeated episodes occurred when fluconazole was administered for periodic mucositis secondary to chemotherapy. The patient had received fluconazole in the past with no difficulty and had been receiving a stable dose of amitriptyline for neuropathic pain. On discontinuation of amitriptyline, no further episodes were noted. DISCUSSION: Concurrent administration of fluconazole with amitriptyline likely resulted in the decreased metabolism of amitriptytine. Three case reports presented in the literature of adults receiving concurrent amitriptyline and fluconazole have shown an increase in serum amitriptyline concentrations with concurrent administration of fluconazole; however, none of these patients were rechallenged. Literature available on amitriptyline overdose confirms that syncope and the adverse events noted in the case studies may result from elevated amitriptyline plasma concentrations. CONCLUSIONS: The consistent presentation of syncope in our patient during readministration of amitriptytine and fluconazole strongly suggests a drug-drug interaction.

Amitriptyline↗
PubMed2001

Efficacy of amitriptyline in the treatment of subjective tinnitus.

We investigated the effect of amitriptyline, a tricyclic antidepressant, on patients with subjective tinnitus. The study group consisted of 37 adult patients admitted to the Ear, Nose, and Throat and Audiology Department of Hacettepe University. The amitriptyline group consisted of 20 patients and the placebo group consisted of 17 patients. All of the patients were evaluated using a questionnaire, audiologic evaluation, high-frequency audiometry, impedancemetric tests, auditory brainstem response, tinnitus frequency, and loudness matching assessed by audiometric methods at the beginning and end of the study. The patients in the amitriptyline group received 50 mg/day amitriptyline in the first week and 100 mg/day for the following 5 weeks. In the placebo group, the patients received tablets consisting of lactose starch for 6 weeks, with a dosage of 1 tablet/day. The subjective complaints of the patients in the amitriptyline group decreased, and the "present" symptoms resulted in fewer complaints. The severity of tinnitus decreased in the amitriptyline group by means of subjective and audiometric methods. In the placebo group, no significant change was observed. The success of treatment was 95% in the amitriptyline group and 12% in the placebo group. Amitriptyline therapy was concluded to be effective.

Adolescent↗
PubMed1998

Diabetic peripheral neuropathy. Effectiveness of electrotherapy and amitriptyline for symptomatic relief.

OBJECTIVE: To evaluate the efficacy of combining electrotherapy with amitriptyline for the management of chronic painful peripheral neuropathy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients (n = 26) with peripheral neuropathy were treated with amitriptyline. After 4 weeks, those patients (n = 23) who failed to respond to amitriptyline or who only had partial relief were randomized between a sham treatment group (control) or an electrotherapy group. Transcutaneous electrotherapy was given for 12 weeks by a portable unit (H-wave machine) that generated a biphasic exponentially decaying waveform (pulse width 4 ms, 25-35 V, > or = 2 Hz). The degree of pain and discomfort was graded on a scale of 0-5. An analog scale was used to record the overall change in symptoms. RESULTS: Amitriptyline produced some degree of symptomatic relief in 15 (60%) of the 26 patients by the 4th week; pain scores decreased from 3.8 +/- 0.1 to 2.9 +/- 0.2 (P < 0.1) and the overall reduction in pain was 26 +/- 5% on an analog scale. In the amitriptyline plus sham treatment group (n = 9), pain scores declined from 2.8 +/- 0.3 to 1.9 +/- 0.5 (P < 0.03) and the overall reduction in pain was 55 +/- 12%, suggesting a procedure-related placebo effect. In the group receiving combined electrotherapy and amitriptyline (n = 14), symptomatic improvement occurred in 12 (85%) patients. Five (36%) of the patients in this group became asymptomatic. Pain scores declined from 3.2 +/- 0.2 to 1.4 +/- 0.4 (P < 0.01) and the overall reduction in pain was 66 +/- 10%. The degree of reduction in pain scores and the incremental relief (above the amitriptyline effect) were significantly greater (P < 0.03) with electrotherapy as compared with sham treatment. The outcomes indicate a substantial beneficial effect of electrotherapy over and above any placebo influence. CONCLUSIONS: Our clinical observations suggest that transcutaneous electrotherapy is effective in reducing the pain associated with peripheral neuropathy. This form of therapy may be a useful adjunctive modality when it is combined with a pharmacological agent, such as amitriptyline, to augment symptomatic relief.

Adult↗
PubMed2005

Amiodarone fails to improve survival in amitriptyline-poisoned mice.

OBJECTIVE: Amiodarone, a class III antidysrhythmic agent, blocks Na+, Ca2+, and K+ channels as well as the beta-adrenergic receptor. Despite increased use of amiodarone for wide-complex tachycardia, its efficacy in the treatment of dysrhythmias induced by tricyclic antidepressants has not been tested. We investigated the effect of amiodarone and amitriptyline in a mouse lethality model. METHODS: The LD50 of amitriptyline obtained from reference sources was confirmed by giving 100 mg/kg to 40 mice by intraperitoneal (IP) injection. The safety of the treatment dose of amiodarone was confirmed by giving 50 mg/kg by IP injection to 10 mice. One hundred and nine mice were randomized to receive pretreatment with 50 mg/kg amiodarone (n=55) or an equal volume of saline or water as a volume control (n=54). Thirty minutes after pretreatment or control injection, the mice received amitriptyline, 100 mg/kg. Outcome was defined as death or survival 3 h after amitriptyline injection. RESULTS: In our confirmation of the LD50 of amitriptyline, 25/40 mice died (62.5%). None of the 10 mice that received only amiodarone died. In the control + amitriptyline arm, 36/54 (66.7%) died, compared with 39/55 (70.9%) in the amiodarone+amitriptyline arm (X2, p=0.663). Power analysis demonstrated a 90% chance of finding a 28% difference. CONCLUSIONS: Pretreatment with amiodarone does not appear to significantly alter the lethality of amitriptyline poisoning in mice. Given the inability to monitor cardiac activity in this model, further investigation in a larger animal is required.

Amiodarone↗
PubMedDate not supplied

Distigmine and amitriptyline in the treatment of chronic pain.

Sixty-five patients attending a pain relief clinic were randomly allocated to treatment for 5 weeks with amitriptyline alone, distigmine alone, amitriptyline and distigmine started together, or addition of distigmine to preexisting treatment with amitriptyline. Forty-eight patients successfully completed the trial; the most common cause for withdrawal was dry mouth in the amitriptyline-alone group. Two parameters were measured: Pain intensity was measured at the beginning and end of the treatment, and the saliva flow was measured at the beginning and the end of the treatment. At the end of 5 weeks, treatment with a combination of amitriptyline (75 mg/day) and distigmine (10 mg/day) resulted in a 43% reduction of pain and no subjectively noticeable mouth dryness. Distigmine alone also decreased pain and increased saliva flow, sometimes to the point of discomfort, whereas amitriptyline alone, in this particular series, did not significantly reduce pain and produced unpleasant mouth dryness. The addition of distigmine to preexisting (and ineffective) amitriptyline treatment failed to relieve pain. We therefore conclude that a combination of amitriptyline and distigmine (both given ab initio) may be a useful therapy for chronic pain.

Adult↗
PubMedDate not supplied

Demethylation and hydroxylation of amitriptyline, nortriptyline, and 10-hydroxyamitriptyline in human liver microsomes.

The rates of demethylation and hydroxylation of amitriptyline, nortriptyline, and 10-hydroxyamitriptyline by microsomes from adult human livers were determined by use of mass-fragmentographic or liquid-chromatographic quantitation of the formed metabolites. The demethylation rates of amitriptyline and 10-hydroxyamitriptyline were higher than the hydroxylation rates of amitriptyline and nortriptyline, especially at high substrate concentration. The amitriptyline demethylation rates were 96-570 and 1750-9230 pmol per mg of protein per 10 min at substrate concentrations of 5 and 100 micro M, respectively. The corresponding rates for the hydroxylations were 43-146 and 305-871, respectively. At high substrate concentration (250 micro M) the curve of concentration vs. rate for 10-hydroxylation of amitriptyline seemed to approach a plateau, whereas those for demethylation did not. Interaction between amitriptyline and nortriptyline at the microsomal level was studied by use of deuterium-labeled amitriptyline, and these two compounds were found to inhibit the hydroxylation of each other. In contrast to hydroxylation, the demethylation of labeled amitriptyline increased upon addition of nortriptyline. These results suggest that the well-established variation in steady-state plasma levels of tricyclic antidepressants is due to interindividual differences in liver enzyme activity.

Amitriptyline↗
PubMedDate not supplied

Effects of imipramine and amitriptyline on intraventricular conduction, effective refractory period, incidence of ventricular arrhythmias induced by programmed stimulation, and on electrocardiogram after myocardial infarction in dog.

The effects of imipramine and amitriptyline on intraventricular conduction, effective refractory period, incidence of ventricular arrhythmias induced by programmed stimulation and on electrocardiogram changes were studied after myocardial infarction in the dog. Amitriptyline, at doses of 1-3 mg/kg, significantly slowed the ventricular conduction of the infarcted zones in a dose- and frequency-dependent manner. Amitriptyline, at doses of 2 and 3 mg/kg, slowed the ventricular conduction slightly in the normal zone. The effective refractory period was prolonged by amitriptyline at a dose of 1 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Amitriptyline, at doses of 1-3 mg/kg, increased heart rate and prolonged the PQ, QRS and QT interval. Imipramine, at a dose of 3 mg/kg, slowed the conduction in infarcted zones to a lesser extent than amitriptyline. Imipramine, at doses of 1 and 2 mg/kg, did not significantly increase the incidence of ventricular arrhythmias. Imipramine, at a dose of 3 mg/kg, prolonged the QRS interval. From the present results it appears that imipramine has a lower cardiac toxicity than amitriptyline.

Amitriptyline↗
PubMed1986

A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia.

Sixty-two patients with fibromyalgia were randomly assigned to receive 25 mg of amitriptyline at night, 500 mg of naproxen twice daily, both amitriptyline and naproxen, or placebo in a 6-week, double-blind trial. Amitriptyline was associated with significant improvement in all outcome parameters, including patient and physician global assessments, patient pain, sleep difficulties, fatigue on awakening, and tender point score. Patients taking the combined naproxen-amitriptyline regimen experienced minor, but not significant, improvement in pain when compared with patients who took amitriptyline alone. Amitriptyline, or amitriptyline and naproxen, is an effective therapeutic regimen for patients with fibromyalgia.

Amitriptyline↗
PubMed1995

Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia.

OBJECTIVE: To determine the prevalence and clinical correlations of an anomaly consisting of electroencephalographic (EEG) waves within the alpha frequency band during non-rapid eye movement (NREM) sleep in patients with fibromyalgia, and to evaluate the alpha NREM sleep anomaly as a predictor of response to amitriptyline. METHODS: Twenty-two patients with fibromyalgia were studied in a 2-month, double-blind, crossover trial of amitriptyline (25 mg/day) versus placebo. Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end of each 2-month treatment period. RESULTS: Six patients (27%) had a clinical response to amitriptyline, while none responded to placebo (P = 0.02). Treatment with amitriptyline or placebo did not result in any changes in the alpha ratings during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly at baseline. Those patients reported more sleep difficulty, but otherwise were clinically indistinguishable from those without this EEG sleep anomaly. Lower baseline alpha NREM sleep ratings were seen in responders to amitriptyline than in nonresponders, but these differences did not reach statistical significance. CONCLUSION: The alpha NREM sleep anomaly is present in only a small proportion of patients with fibromyalgia. It does not correlate with disease severity nor is it affected by treatment with amitriptyline. A larger sample size will be needed to adequately assess the value of this sleep anomaly in predicting the response to amitriptyline.

Adult↗
PubMed1979

A method for the determination of amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma using stable isotope dilution and gas chromatography-chemical ionization mass spectrometry (GC-CIMS).

A gas chromatography--mass spectrometry (GC-MS) method has been developed to measure amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma. Deuterated analogs of each compound were synthesized as internal standards. Isobutane was used as both gas chromatography (GC) carrier gas and chemical ionization (CI) reagent gas. In order to obtain compounds with satisfactory GC and mass spectrometry (MS) properties, the two alcohol metabolites were dehydrated without loss of label during sample preparation. Selective ion monitoring of the MH+ ions of the protio- and deuterio- compounds gave ion ratios which were converted to plasma concentrations using standard curves. For amitriptyline and nortriptyline, which are assayed using multiple deuterated analogs as internal standards, the curves are straight lines. For 10-hydroxyamitriptyline and 10-hydroxynortriptyline, which are assayed using monodeuterated analogs as internal standards, the curves are nonlinear and are analyzed using an iterative computer procedure. Assay sensitivity is 0.5 ng/ml for amitriptyline, nortriptyline, and 10-hydroxyamitriptyline and 1 ng/ml for 10-hydroxynortriptyline. Assay precision and accuracy in terms of percent error are both less than 5%. Following oral administration of a single 75-mg dose of amitriptyline to two subjects, the mean plasma levels of amitriptyline, nortriptyline, 10-hydroxyamitriptyline, conjugated 10-hydroxyamitriptyline, 10-hydroxynortriptyline, and conjugated 10-hydroxynortriptyline were 36, 8, 10, 66, 16, and 46 ng/ml, respectively, at 2 hr after dosing and 3, 4, 0.5, 1, 6, and 17 ng/ml, respectively, at 72 hr after dosing. Analyses of plasma samples from 12 subjects who had been receiving 50 mg amitriptyline therapy three times a day for an average +/- SD of 32 +/- 5 days gave a mean concentration of 81 +/- 40 ng/ml for amitriptyline, 71 +/- 57 ng/ml for nortriptyline, 12 +/- 5 ng/ml for 10-hydroxyamitriptyline, 91 +/- 30 ng/ml for conjugated 10-hydroxyamitriptyline, 82 +/- 27 ng/ml for 10-hydroxynortriptyline, and 176 +/- 64 ng/ml for conjugated 10-hydroxynortriptyline.

Amitriptyline↗
PubMed2001

Micropolarity and microviscosity of amitriptyline and dextran sulfate/carrageenan-amitriptyline systems: the nature of polyelectrolyte-drug complexes.

The polarity and viscosity of the microenvironment of aggregates of the cationic amphiphilic drug amitriptyline and dextran sulfate (DxS)/carrageenan-amitriptyline aggregates in aqueous solution were investigated by means of steady state and time-resolved fluorescence. For the latter systems, equilibrium dialysis and capillary viscometry were also used. The micropolarity as detected by pyrene indicated the formation of amitriptyline aggregates, both with and without polyelectrolyte, having properties similar to "traditional" cationic micelles. The pyrene lifetime in the amitriptyline- and amitriptyline-polyelectrolyte aggregates was long ( approximately 230 and approximately 300 ns, respectively), indicating that pyrene was well protected from oxygen quenching, especially so in the latter case. The microviscosity of the amitriptyline aggregates themselves, and in the presence of polyelectrolyte, was high, as indicated by intramolecular excimer formation of 1,3-di(1-pyrenyl)-propane (P3P), rotational diffusion fluorescence depolarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), and intramolecular rotational relaxation about bonds of [p-(dimethylamino)benzylidene]-malonitrile (BMN). These results and the concurrent decrease of the bulk viscosity indicate that the polyelectrolyte, acting as polycounterion, is tightly wrapped around the amitriptyline aggregates. Amitriptyline hence behaves in accordance with accepted models of cationic surfactant-polyelectrolyte interaction.

Amitriptyline↗
PubMed1994

Tranylcypromine does not enhance the effects of amitriptyline on 5-HT2 receptors in rat cerebral cortex.

The combination of amitriptyline (a tricyclic antidepressant) and tranylcypromine (a monoamine oxidase inhibitor) has been reported to be effective for treatment of refractory depressed patients. In the study reported here, this drug combination was compared with amitriptyline administered alone on the number and affinity of 5-HT2 receptors in rat brain. Male Sprague-Dawley rats were given vehicle (distilled water), amitriptyline (3.5 mg/kg/day), or tranylcypromine and amitriptyline (0.5 and 3.5 mg/kg/day, respectively) in combination subcutaneously via osmotic minipumps for 4, 10, or 28 days. A membrane fraction prepared from whole cortex was employed for studying binding to 5-HT2 receptors ([3H]ketanserin as the radioligand). The combination of amitriptyline and tranylcypromine produced a small but significantly greater down-regulation (decrease in number) of 5-HT2 sites than did amitriptyline alone after 10 days of administration; at 4 and 28 days, both amitriptyline and the drug combination had produced down-regulation, but there was not a significant difference between the two treatments. These data suggest that the antidepressant efficacy observed with this combination is not likely due to an enhanced effect on 5-HT2 receptors.

Amitriptyline↗