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PubMed1996

Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states.

Amitriptyline is a tricyclic antidepressant agent which also has analgesic properties. Whether its analgesic effects are linked to its mood-altering activity or attributable to a discrete pharmacological action (or a combination of both) is unknown. Clinical trials demonstrate that oral amitriptyline achieves at least a good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups of patients with chronic non-malignant pain. Other possible areas of use for amitriptyline are in patients with fibromyalgia or as an adjuvant for uncontrolled cancer pain, although evidence for the latter application is limited. Adverse events resulting from the antimuscarinic activity of amitriptyline (primarily dry mouth and sedation) are commonly reported, even at the low dosages used for the control of pain. Low starting doses and careful dosage titration may help to minimise these effects. Orthostatic hypotension and tachycardia, sometimes associated with tricyclic antidepressant agents, may also pose a problem in the elderly. In summary, amitriptyline has a valuable place in the treatment of chronic pain conditions that affect the elderly provided that the drug is used judiciously to minimise adverse effects. Importantly, amitriptyline remains the best studied of the antidepressant agents in post-herpetic neuralgia and diabetic neuropathy and is an important and effective treatment option in these syndromes.

Aged↗
PubMedDate not supplied

Amitriptyline dosage prediction in elderly patients from plasma concentration at 24 hours after a single 100mg dose.

Fifteen depressed elderly patients (14 female, 1 male; mean age 85 years) received a single oral dose of amitriptyline. The concentration of amitriptyline plus nortriptyline in a blood sample taken 24 hours later was used to predict by means of a nomogram the amitriptyline dosage required for each patient. Each dose was selected to produce steady-state amitriptyline plus nortriptyline concentrations close to 140 micrograms/L. The daily dosage ranged from 20 to 100mg (mean 62mg). Patients received the individually calculated dose each night, and weekly blood samples were obtained for drug analysis. At 2 weeks, mean amitriptyline plus nortriptyline concentrations were 118 +/- 21 micrograms/L. Eight of the patients were studied for a further 2 weeks and the mean amitriptyline plus nortriptyline concentration was then 111 +/- 19 micrograms/L. The dose prediction test is easy to use and ensures each patient receives an adequate but safer dose of amitriptyline than might otherwise be prescribed routinely.

Aged↗
PubMed1991

Comparison of adinazolam, amitriptyline, and diazepam in endogenous depressive inpatients exhibiting DST nonsuppression or abnormal contingent negative variation.

Adinazolam, a triazolobenzodiazepine that has an action similar to antidepressants in several pharmacological tests, was compared with amitriptyline and diazepam in endogenous depressive inpatients exhibiting dexamethasone suppression test non-suppression and/or abnormal contingent negative variation. Three parallel groups of 22 patients received in double-blind conditions either adinazolam (60-90 mg/day), amitriptyline (150-225 mg/day), or diazepam (30-45 mg/day) over a 4-week period, with weekly assessments by the Hamilton Rating Scale for Depression. Results showed significant superiority of amitriptyline over diazepam on total Hamilton depression scores. On the endogenomorphy subscale, amitriptyline induced significantly better improvement than both diazepam and adinazolam, whereas both amitriptyline and adinazolam exhibited significantly better antidepressant efficacy on the core symptoms of depression. Moreover, the dropout rate for inefficacy after 2 weeks of treatment was higher in the diazepam group. Taken together, these findings suggest that adinazolam has an antidepressant efficacy intermediate between amitriptyline and diazepam. Adinazolam was, however, much better tolerated than amitriptyline, and produced significantly fewer anticholinergic side effects.

Adult↗
PubMedDate not supplied

Comparison of the cardiac electrophysiologic effects of amitriptyline and clomipramine in the dog after myocardial infarction.

The effects of the tricyclic antidepressants amitriptyline and clomipramine on intraventricular conduction, effective refractory period and incidence of ventricular arrhythmias induced by programmed stimulation, were studied in the dog heart after myocardial infarction. Amitriptyline, at doses of 1 to 3 mg/kg, significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and a dose-dependent manner. Amitriptyline, at doses of 2 and 3 mg/kg, slightly slowed conduction in normal zones. The effective refractory period was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. On the other hand, the depressant effect of clomipramine, at doses of 1 to 3 mg/kg, on the conduction of infarcted zones was lower than that of amitriptyline, whereas the severely depressed conduction in the infarcted zone was obviously slowed by clomipramine. The incidence of ventricular arrhythmias did not significantly increase with clomipramine. From the present results, clomipramine seems to have a lower cardiac toxicity than amitriptyline, although clomipramine produces a slight depression of conduction in infarcted zones.

Amitriptyline↗
PubMedDate not supplied

Some effects of desmethylimipramine and amitriptyline on the schedule-controlled behavior of pigeons and rats.

The effects of desmethylimipramine and amitriptyline on schedule-controlled behavior of pigeons and rats were examined. Pigeons responded under either a multiple (mult) fixed-interval (FI) 600-sec, fixed-ratio (FR) 30-response schedule of food presentation or a mult FI 200-sec, FI 200-sec schedule, in which responding during one component was punished with electric shock. Rats responded under a mult FI 300-sec, FR 30-response schedule of food presentation. Under the mult FI, FR schedules, desmethylimipramine and amitriptyline decreased overall rates of FI and FR responding in both species. Overall rates of responding were decreased to similar extents under both the FI and FR components of the schedule. In the pigeon, but not in the rat, the effects of desmethylimipramine and amitriptyline on responding under the FI component of the mult FI, FR schedule depended on the control-rate of responding, i.e. desmethylimipramine and amitriptyline increased more or decreased less the low rates of FI responding at the beginning of the FI compared to the higher rates of FI responding at the end of the FI. In contrast, in the rat desmethylimipramine and amitriptyline did not differentially affect the low rates of responding at the beginning of the FI compared to the higher rates of responding at the end of the FI. Correspondingly, in the pigeon, but not in the rat, desmethylimipramine and amitriptyline decreased the fixed-interval quarter-life at relatively low doses. In the pigeon neither desmethylimipramine nor amitriptyline differentially affected the overall rate of punished as compared to unpunished responding.

Amitriptyline↗
PubMed1984

Treatment of ventricular tachyarrhythmias resulting from amitriptyline toxicity in dogs.

This study was designed to analyze the effects of lidocaine and sodium bicarbonate on ventricular arrhythmias resulting from amitriptyline infusion in dogs. Amitriptyline was infused i.v. at 0.5 mg/kg/min for 30 min, followed by 1 mg/kg/min to dogs anesthetized with morphine and alpha-chloralose. When arrhythmia occurred, the infusion rate was reduced by one-third and the effect of various interventions studied. In the initial 18 dogs, lidocaine, sodium bicarbonate or isotonic saline was administered i.v. to six dogs each in a randomized, blinded fashion. The prevalence of ventricular ectopic complexes was not changed after isotonic saline, but was reduced by lidocaine at concentrations greater than or equal to 5 mg/l and by sodium bicarbonate. The effects of lidocaine were transient and associated with significant blood pressure reduction. Sodium bicarbonate produced more dramatic and sustained arrhythmia reversal along with a reduction in amitriptyline-induced conduction slowing. Administration of hypertonic sodium chloride in equimolar quantities to sodium bicarbonate failed to affect amitriptyline-induced ventricular arrhythmias significantly, but hyperventilation to a pH similar to that produced by sodium bicarbonate (7.48) significantly reduced the frequency of amitriptyline-induced ventricular ectopy. When amitriptyline was infused into dogs ventilated with various respiratory rates, ventricular arrhythmia resulted in 18 of 18 (100%) dogs with pH less than 7.42, 2 of 4 (50%) dogs with pH between 7.48 and 7.51 and 0 of 8 (0%) dogs with a pH between 7.59 and 7.65 (P less than or equal to .001). These results suggest that sodium bicarbonate is effective treatment for amitriptyline-induced cardiac arrhythmias with beneficial effects largely due to alkalinization.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗
PubMed1982

Quantitative assessment of the pre- and postsynaptic alpha adrenoceptor antagonist potency of amitriptyline.

The pre- and postsynaptic alpha adrenoceptor blocking affinity of amitriptyline was determined in isolated tissues by Schild regression analysis. In the absence of uptake-1 blockade with cocaine, amitriptyline treatment (3 X 10(-8)-3 X 10(-6) M) affected only marginally norepinephrine concentration-response curves in the rat anococcygeus muscle; a result suggesting opposing pharmacological effects (uptake-1 blockade and alpha blockade). After cocaine (3 X 10(-5) M) treatment, amitriptyline (3 X 10(-8)-3 X 10(-6) M) antagonized competitively concentration-response curves to norepinephrine, yielding a postsynaptic pKb of 7.51. A similar pKb was obtained when methoxamine was the agonist. Presynaptic alpha blocking affinity was determined by using the field-stimulated rat vas deferens. Stimulus conditions were chosen which minimized the inhibition of twitch height by high concentrations of cocaine. Using these conditions (10 Hz, 200 msec duration at 100-sec intervals), amitriptyline antagonized competitively clonidine inhibition of field-stimulated twitch contractions, yielding at pKb of 5.23. The presynaptic pKb was not changed in the presence of theophylline (10(-4) M). Amitriptyline was also observed to increase the release of [3H]norepinephrine from the field-stimulated rat anococcygeus muscle pretreated with cocaine. Although this effect primarily reflects alpha blockade, other biochemical and presynaptic mechanisms may be involved. Comparing the pre- and postsynaptic alpha blocking affinities indicates that amitriptyline has 191 X greater affinity for post- than presynaptic alpha adrenoceptors (i.e., alpha-1 much greater than alpha-2). The relevance of these observations to the mechanism of action and side effects of amitriptyline are discussed.

Adrenergic alpha-Antagonists↗
PubMed1980

Interaction of the tricyclic antidepressant amitriptyline with prejunctional alpha and muscarinic receptors in the dog saphenous vein.

Amitriptyline can cause tachycardia and arrhythmia associated with an excessive release of cardiac catecholamines. We have investigated its effects on norepinephrine release from adrenergic nerves by using the dog saphenous vein as a model of the sympathetic neuroeffector junction. Isolated strips of vein were mounted for isometric tension recording or incubated with [3H]norepinephrine and mounted for superfusion, tension recording and the superfusate. Amitriptyline (10(-6); 5 x 10(-6) M) increased the overflow of [3H]norepinephrine but decreased that of [3,4-3H]dihydroxyphenylglycol from electrically stimulated strips. The selective decreased in the overflow of this metabolite indicates that amitriptyline inhibits neuronal uptake. However, the increased overflow of [3H]norepinephrine caused by amitriptyline also occurred when neuronal uptake was blocked by cocaine (3 x 10(-5) M) but was abolished when prejunctional alpha receptors were blockade by phentolamine (10(-5) M). Amitriptyline attenuated the prejunctional inhibitory action of exogenous norepinephrine, this indicates that the drug interacts with prejunctional alpha receptors. Amitriptyline also antagonized the prejunctional inhibitory action of acetylcholine, both in the absence and presence of cocaine and phentolamine. These effects were not due to a nonspecific action of the drug as it did not reduce the prejunctional inhibitory effect of histamine. Thus, amitriptyline can increase the concentration of norepinephrine at the neuroeffector junction by blockade of neuronal uptake and by interacting with prejunctional alpha and muscarinic receptors. Since the cardiac adrenergic nerves also possess these receptors, the results could help to explain the cardiotoxic effects of the drug.

Amitriptyline↗
PubMed1978

The kinetics of amitriptyline following single oral dose administration to man.

Amitriptyline and its metabolite, nortriptyline, were measured in the plasma of eight humans for 96 hours following oral administration of a 75 mg dose of amitriptyline hydrochloride. Based on the 8 to 96 hour post dosing plasma concentration data, the terminal exponential half life of amitriptyline +/- S.D. was 22.4 +/- 4.3 hr. Based on the 24 to 96 hour concentration data, the "apparent" terminal half time of nortriptyline +/- S.D. was 26.0 +/- 7.4 hours for seven subjects. For these same seven subjects the relative area under the plasma concentration time curve of nortriptyline +/- S.D. was only 0.88 +/- 0.34 times that of amitriptyline. One subject whose apparent nortriptyline half time was 108 hours had a nortriptyline bioavailability 3.83 times that of amitriptyline. Average steady state plasma levels for 12 psychiatric patients who had received a 50 mg oral dose of amitriptyline three times a day for an average of 32 days could be predicted from the single dose plasma clearance of amitriptyline.

Adult↗
PubMedDate not supplied

Spinal manipulation vs. amitriptyline for the treatment of chronic tension-type headaches: a randomized clinical trial.

OBJECTIVE: To compare the effectiveness of spinal manipulation and pharmaceutical treatment (amitriptyline) for chronic tension-type headache. DESIGN: Randomized controlled trial using two parallel groups. The study consisted of a 2-wk baseline period, a 6-wk treatment period and a 4-wk posttreatment, follow-up period. SETTING: Chiropractic college outpatient clinic. PATIENTS: One hundred and fifty patients between the ages of 18 and 70 with a diagnosis of tension-type headaches of at least 3 months' duration at a frequency of at least once per wk. INTERVENTIONS: 6 wk of spinal manipulative therapy provided by chiropractors or 6 wk of amitriptyline treatment managed by a medical physician. MAIN OUTCOME MEASURES: Change in patient-reported daily headache intensity, weekly headache frequency, over-the-counter medication usage and functional health status (SF-36). RESULTS: A total of 448 people responded to the recruitment advertisements; 298 were excluded during the screening process. Of the 150 patients who were enrolled in the study, 24 (16%) dropped out: 5 (6.6%) from the spinal manipulative therapy and 19 (27.1%) from the amitriptyline therapy group. During the treatment period, both groups improved at very similar rates in all primary outcomes. In relation to baseline values at 4 wk after cessation of treatment, the spinal manipulation group showed a reduction of 32% in headache intensity, 42% in headache frequency, 30% in over-the-counter medication usage and an improvement of 16% in functional health status. By comparison, the amitriptyline therapy group showed no improvement or a slight worsening from baseline values in the same four major outcome measures. Controlling for baseline differences, all group differences at 4 wk after cessation of therapy were considered to be clinically important and were statistically significant. Of the patients who finished the study, 46 (82.1%) in the amitriptyline therapy group reported side effects that included drowsiness, dry mouth and weight gain. Three patients (4.3%) in the spinal manipulation group reported neck soreness and stiffness. CONCLUSIONS: The results of this study show that spinal manipulative therapy is an effective treatment for tension headaches. Amitriptyline therapy was slightly more effective in reducing pain at the end of the treatment period but was associated with more side effects. Four weeks after the cessation of treatment, however, the patients who received spinal manipulative therapy experienced a sustained therapeutic benefit in all major outcomes in contrast to the patients that received amitriptyline therapy, who reverted to baseline values. The sustained therapeutic benefit associated with spinal manipulation seemed to result in a decreased need for over-the-counter medication. There is a need to assess the effectiveness of spinal manipulative therapy beyond four weeks and to compare spinal manipulative therapy to an appropriate placebo such as sham manipulation in future clinical trials.

Adult↗
PubMed1995

Biotransformation of amitriptyline by Cunninghamella elegans.

A fungal biotransformation system as an in vitro model for mammalian drug metabolism was investigated. Amitriptyline, a widely used antidepressant, was effectively biotransformed within 72 hr by the filamentous fungus, Cunninghamella elegans. Eight major metabolites in HPLC elution order (11-hydroxyamitriptyline N-oxide, 11-hydroxynortriptyline, 11-hydroxyamitriptyline, 10-hydroxyamitriptyline, 3-hydroxyamitriptyline, 2-hydroxyamitriptyline, nortriptyline, and amitriptyline N-oxide) were produced at estimated molar ratios of 2:1:10:0.6:0.1:1.2.5:0.5, respectively. These metabolites were isolated by HPLC and identified by UV/MS analyses, as well as NMR spectroscopic analysis for most of these metabolites. In some cases, they were also compared with authentic standards. Glucose, culture age, and substrate concentration significantly affected the extent of amitriptyline metabolism. Kinetic studies indicated that nortriptyline and 11-hydroxyamitriptyline were produced as initial major metabolites. The hydroxylated metabolite was excreted from mycelia, but amitriptyline and its N-demethylated metabolite, nortriptyline, were not. An 18O2 labeling experiment showed that the oxygen atoms in 11-hydroxyamitriptyline and 2-hydroxyamitriptyline were derived from molecular oxygen. The cytochrome P450 inhibitors SKF 525-A (1.5 mM), metyrapone (2.0 mM), and 1-aminobenzotriazole (1.0 mM) inhibited the biotransformations of amitriptyline by 50, 75, and 95%, respectively. A microsomal preparation was shown to catalyze the 11-hydroxylation of amitriptyline, which was inhibited by SKF 525-A and carbon monoxide. The similarities of amitriptyline metabolism in C. elegans and in humans and rats are discussed.

Amitriptyline↗
PubMed1996

Regulation of extracellular concentrations of norepinephrine in hypothalamus of the conscious rat: effect of amitriptyline.

The current study examines the effects of amitriptyline administration on extracellular levels of monoamines and their metabolites in hypothalamus of conscious rat using in vivo microdialysis. Systemic amitriptyline (30 mg/kg, i.p.) maximally increased extracellular norepinephrine to nearly 19 times, dopamine 12 times, and serotonin 2.5 times that of their respective basal values. Local administration of amitriptyline (10 microM) in the perfused artificial cerebrospinal fluid increased extracellular serotonin levels to 2.7 times basal levels - a similar increase to that observed with systemic administration. In contrast, local administration of amitriptyline (10 microM) increased extracellular norepinephrine and dopamine to only 5.3 and 3.8 times basal levels. Systemic administration of amitriptyline (30 mg/kg, i.p.) during local amitriptyline perfusion increased norepinephrine and dopamine levels to 28 and 12.9 times their respective basal levels without affecting serotonin levels. Systemic amitriptyline administration preferentially increases extracellular norepinephrine and dopamine levels over serotonin levels in the rat hypothalamus and the effects on the catecholamine levels may be partially due to mechanisms other than local uptake inhibition.

Amitriptyline↗
PubMed1979

Amitriptyline in migraine prophylaxis.

In a controlled trial of amitriptyline hydrochloride in migraine prophylaxis, 100 patients received placebo for a four-week baseline period and then were randomized in double-blind fashion to therapy with amitriptyline (47 subjects) or placebo (53 subjects) for another four to eight weeks. Subjects received up to four 25-mg tablets of amitriptyline hydrochloride or identical placebo per day. Comparing the first and second four-week periods for each patient, the conditions of 55.3% of amitriptyline subjects as opposed to 34.0% of placebo subjects were greater than or equal to 50% improved and the difference between amitriptyline and placebo response rates was significant (P less than .05). Nondepressed subjects with severe migraine and depressed subjects with less severe migraine responded best to amitriptyline, whereas depressed subjects with severe migraine had little headache relief. Amitritryline is an effective antimigraine agent and the antimigraine effect seems relatively independent of antidepressant activity.

Amitriptyline↗
PubMed1984

Serotonin function and mechanism of action of antidepressant treatment. Effects of amitriptyline and desipramine.

The effects of amitriptyline hydrochloride and desipramine hydrochloride treatment on brain serotonin (5-HT) function were investigated in 21 patients. The ability of an intravenous infusion of the serotonin precursor tryptophan to raise serum prolactin (PRL) levels was determined in 13 depressed patients during placebo administration and after 28 to 35 days of treatment with either amitriptyline or desipramine. Both desipramine (N = 7) and amitriptyline (N = 6) significantly increased the PRL rise induced by tryptophan compared with a preceding placebo period. In contrast, following long-term amitriptyline and desipramine treatment, the ability of tryptophan to increase PRL was enhanced two weeks following abrupt cessation of amitriptyline therapy (N = 5), but not after discontinuation of desipramine therapy. The results of this investigation are consistent with electrophysiologic and behavioral studies in laboratory rats and suggest that desipramine- and amitriptyline-induced alterations in 5-HT function may be related to their antidepressant mechanism of action.

Aged↗
PubMed1986

Progress in pharmacotherapy of borderline disorders. A double-blind study of amitriptyline, haloperidol, and placebo.

In symptomatic patients with borderline disorder, we conducted a double-blind, placebo-controlled trial of haloperidol and amitriptyline hydrochloride to test the differential efficacy of medication against the affective and schizotypal symptoms that characterize the disorder. Sixty-one patients, diagnosed by the Diagnostic Interview for Borderline of Gunderson et al, completed randomized trials of haloperidol (n = 21), amitriptyline (n = 20), and placebo (n = 20). Medications were given in dose ranges of 4 to 16 mg for haloperidol (mean, 7.24 mg) and 100 to 175 mg for amitriptyline hydrochloride (mean, 147.62 mg) for five-week periods, with weekly self-rated and observer-rated measures of mood, schizotypal symptoms, and global functioning. Haloperidol was superior to both amitriptyline and placebo on a composite measure of overall symptom severity, with no difference between amitriptyline and placebo. Haloperidol produced significant improvement on a broad spectrum of symptom patterns, including depression, anxiety, hostility, paranoid ideation, and psychoticism. In contrast, amitriptyline was minimally effective, with small gains limited to some areas of depressive content. The magnitude of change tended to be modest and was more apparent in self-rated than observer-rated measures.

Adolescent↗
PubMed2003

Mirtazapine in combination with amitriptyline: a drug-drug interaction study in healthy subjects.

OBJECTIVE: To assess the steady-state pharmacokinetics of mirtazapine (30 mg/day orally) and amitriptyline (75 mg/day orally) during combined administration compared with that of either drug administered alone. To evaluate the tolerability and effects on psychometric tests of acute and subchronic administration of both drugs combined and alone. METHODS: In a single-blind, three-way cross-over study, 24 (12 male and 12 female) healthy subjects were randomly assigned to six different sequences of three 9-day treatments, i.e. racemic mirtazapine (30 mg/day), amitriptyline (75 mg/day) or the combination of these drugs. To control for acute pharmacodynamic assessments, during the first treatment period, a placebo group (n = 8; 4 females and 4 males) was added. Serial blood samples were drawn for plasma level measurements that were subsequently subjected to pharmacokinetic analysis. Psychometric tests assessed attentional performance, and a computer-assisted telephone questionnaire assessed self-ratings of drowsiness/alertness and sleep quality. RESULTS: Amitriptyline increased the C(max) of mirtazapine (+ 36%, p < 0.05) in male subjects only. Mirtazapine altered the C(max) of amitriptyline in both male (+ 23%, p < 0.05) and female (- 23%, p < 0.05) subjects. No changes were observed for other pharmacokinetic parameters. Metabolite parameters were not affected. Changes in parent compound levels mainly resulted from effects on absorption. The psychometric test results did not reveal significant changes between combined and single drug treatments. The telephone registrations of VAMRS and LSEQ did not show clinically relevant differences between the active treatments. CONCLUSION: Combined administration of mirtazapine (30 mg/day) and amitriptyline (75 mg/day) alters the pharmacokinetics of either compound to a minor extent. Adding one drug to the other and substituting one drug by the other had no major effects on tolerability. Nevertheless, caution is warranted when combining amitriptyline and mirtazapine.

Adolescent↗
PubMed1986

Inhibition of head twitch response to quipazine in rats by chronic amitriptyline but not fluvoxamine or citalopram.

Chronic (twice daily/14 days), but not acute, treatment with 10 mg/kg PO amitriptyline reduced the number of quipazine (5 mg/kg)-induced head twitches in rats, measured 2 h (but not 72 h) after the last administration of the drug. Similar treatment with fluvoxamine or citalopram, which are more potent and much more specific serotonin uptake inhibitors than amitriptyline, did not affect the quipazine-induced response. In acute experiments, fluvoxamine (10 mg/kg PO) and citalopram (10 mg/kg PO) potentiated the head twitch reaction induced by L-5-hydroxytryptophan (50 mg/kg IP) given together with Ro 4-4602 (25 mg/kg IP), a peripheral decarboxylase inhibitor. Amitriptyline (10 mg/kg PO) slightly decreased the number of L-5-hydroxytryptophan (5-HTP)-induced head twitches. Higher doses of amitriptyline (20-40 mg/kg PO) also inhibited the quipazine-induced head twitch reaction. The brain level of amitriptyline measured 0.5-24 h after the last oral administration of the chronic dose of 10 mg/kg was always much higher than that observed at the same time intervals after an acute oral dose of 20 or 40 mg/kg. The results obtained indicate that a postsynaptic rather then presynaptic mechanism is responsible for the development of subsensitivity of the central serotonin receptors in the course of chronic treatment with amitriptyline.

5-Hydroxytryptophan↗
PubMed1991

Echocardiographic and psychometric effects of amitriptyline or imipramine plus alcohol.

The echocardiographic and psychometric effects of amitriptyline or imipramine combined with alcohol have been studied in a double-blind cross-over trial in 7 healthy volunteers. Amitriptyline or imipramine 25 mg b.d. were given for three days and then the dose was doubled. On Days 1 and 10-13 echocardiographic measurements were done, and on Day 15 psychomotor tests were performed. Ethanol 1 g/kg in each session was administered 1 h after drug intake. Alcohol alone increased heart rate and decreased the systolic blood pressure and ejection fraction. It also impaired most of the psychomotor measures, horizontal nystagmus being the most sensitive test. On Day 1, the first dose of imipramine decreased the heart rate and increased diastolic blood pressure. These effects were partly counteracted by alcohol. Imipramine + alcohol decreased the WSTR. Amitriptyline alone did not affect the echocardiographic findings on Day 1. In combination with alcohol it reduced cardiac output and prolonged PEP, and increased the PEP/LVET ratio. During subacute treatment (Days 10-13) WSTR was increased by both antidepressants, but only amitriptyline increased the heart rate. Unlike imipramine + alcohol, amitriptyline + alcohol decreased WSTR and MCSR. Digit symbol substitution was the only pschometric test in which the alcohol effect was clearly enhanced by both amitriptyline and imipramine.

Administration, Oral↗