Arzneimittelforschung. 1984;34(10):1258-60.
[Inhibition of monoamine oxidase A and B in the heart and brain of the rat with amitriptyline, pargyline and pirlindol]

[Article in German]

Schraven E, Reibert R.

The inhibition of monoamine oxidase (MAO) A and B by amitriptyline, pargyline and pirlindole was measured in heart and brain homogenates of rats with tryptamine and beta-phenylethylamine as substrates. The tricyclic antidepressant amitriptyline inhibited MAO B stronger in the brain (Ki = 8.41 X 10(-6) mol/l) as well as in the heart (Ki = 7.03 X 10(-5) mol/l) compared to the A-form (1.51 X 10(-4) and 1.03 X 10(-4) mol/l, respectively). Pargyline diminished the activity of both enzyme forms of the heart in the same range (4.29 and 1.60 X 10(-6) mol/l), whereas in the brain the B-form was blocked in a more pronounced manner, too (5.80 X 10(-8) and 4.01 X 10(-6) mol/l, respectively). In contrast to amitriptyline and pargyline pirlindole inhibited the MAO with tryptamine as a substrate in the brain 100 times (2.49 X 10(-7) mol/l) and in the heart nearly 1000 times (3.42 X 10(-8) mol/l) more than with phenylethylamine as a substrate (5.21 and 5.99 X 10(-5) mol/l, respectively). These results show that amitriptyline and pargyline are relatively selective inhibitors of MAO B, whereas pirlindole blocks the A-form of MAO much stronger than MAO B.

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Jpn J Pharmacol. 1987 Nov;45(3):335-42.
Cardiovascular effects of paroxetine, a newly developed antidepressant, in anesthetized dogs in comparison with those of imipramine, amitriptyline and clomipramine.

Yokota S, Ishikura Y, Ono H.

Department of Pharmacology and Toxicology, Hatano Research Institute, Kanagawa, Japan.

The cardiovascular effects of various antidepressant drugs including paroxetine, imipramine, amitriptyline and clomipramine, administered intravenously, have been assessed. Paroxetine, imipramine, amitriptyline or clomipramine potentiated the response to norepinephrine (0.1 microgram/kg, i.v.) on systemic blood pressure, while paroxetine, imipramine and amitriptyline weakened the response to tyramine (30 micrograms/kg, i.v.). A marked decrease in systemic blood pressure was observed after large doses of each drug (3 and 10 mg/kg of paroxetine; 1-10 mg/kg of imipramine, amitriptyline or clomipramine); and half of the animals died following administration of 10 mg/kg of imipramine, amitriptyline or clomipramine. Paroxetine did not show a marked effect on heart rate at a dose of up to 3 mg/kg, although 0.1-3 mg/kg of imipramine, amitriptyline or clomipramine dose-dependently caused tachycardia. ECG disturbances were observed in animals administered 10 mg/kg of imipramine, amitriptyline or clomipramine; but in contrast, 10 mg/kg of paroxetine caused only slight changes in the ECG. Prolongation of atrio-ventricular conduction time was observed with all the drugs. It was concluded that the effects of paroxetine on the canine heart are more mild in comparison with other tricyclic antidepressants used, although its pharmacological features are essentially similar to those of other drugs.

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Neuropsychobiology. 1986;15(1):15-9.
Biotransformation of amitriptyline in man: interaction with phenothiazines.

Vandel S, Sandoz M, Vandel B, Bonin B, Allers G, Volmat R.

The biotransformation modification of amitriptyline by phenothiazines has been studied in 65 depressive inpatients. Thirty-four of them were treated with oral amitriptyline and 31 with a combination of amitriptyline and phenothiazine. Urinary and plasmatic results showed a decrease in hydroxylated metabolites of amitriptyline (OHAMTc and OHAMT) in patients with added phenothiazine.

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Psychiatr Clin (Basel). 1976;9(1):5-13.
[Individual conditions of pharmacogenic confusion conditions. Comparison of amitriptyline and clozapine]

[Article in German]

Gabriel E, Kufferle B, Lenz G, Schuster P.

The literature was surveyed concerning the frequency and conditions for confusional states and deliria following Amitriptyline and Clozapine treatment, and certain discrepancies were noted. As a result a retrospective comparative investigation was carried out as to the frequency and the conditions for such events in a group of patients treated along the same lines. While our experience with Amitriptyline is not different from that reported by others, this does not seem to be the case with Clozapine. Confusional states and deliria are four times as frequent as the average reported in the literature; it is clear that they depend on conditions different from those of confusional states and deliria due to Amitriptyline; there is a slightly significant (p less than 0.05) correlation between the appearance of confusion and a temperature of over 37.5 degrees C. The anticholinergic properties of Amitriptyline and of Clozapine cannot explain the difference in frequency, nor the differing conditions for the appearance, of pharmacogenic confusional states and deliria with those two substances.

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Pharmacopsychiatry. 1985 Jul;18(4):259-62.
Single oral dose pharmacokinetics of amitriptylinoxide and amitriptyline in humans.

Kuss HJ, Jungkunz G, Johannes KJ.

Eleven healthy volunteers were examined in a pharmacokinetic study. After oral administration of 50 mg amitriptylinoxide or 50 mg amitriptyline the plasma levels of amitriptylinoxide and its main metabolites amitriptyline and nortriptyline were investigated over 24 hours. The results indicate that amitriptylinoxide is more rapidly absorbed than amitriptyline and eliminated with a mean half-life of 1.5 hours. The change with time in the levels of amitriptyline formed from the oxide is similar to that of amitriptyline after ingestion of amitriptyline. However, the plasma concentration of amitriptylinoxide, reflected by the area under the time curve (AUC), exceeds that of its metabolite amitriptyline twelvefold.

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Eur J Clin Pharmacol. 1983;25(3):325-31.
Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction.

Dorian P, Sellers EM, Reed KL, Warsh JJ, Hamilton C, Kaplan HL, Fan T.

Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyline free plasma concentrations were increased by a logarithmic mean of 204%, 186% and 127% at 1.5, 2, and 2.5 h, respectively, and amitriptyline free AUC0-8h was increased by 48% +/- 13% (means +/- SEM) (t = 5.21, p less than 0.01). Nortriptyline total AUC0-8h was increased by 26.6% +/- 12% (means +/- SEM) (t = 2.21, p less than 0.09). At the time of peak amitriptyline plasma concentrations, mean postural sway was increased over baseline by 92% with, and 2% without ethanol; likewise, mean short term memory (word recall) was decreased over baseline by 71% with, and 37% without ethanol. Ethanol increases free amitriptyline plasma concentrations most dramatically during the period of drug absorption; this is due to a decrease in amitriptyline hepatic clearance, resulting in decreased first-pass extraction. Together with the pharmacodynamic interaction, the kinetic changes provide a rationale for the toxicity of this combination and its deleterious effects on psychomotor skills.

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J Clin Psychiatry. 1980 Oct;41(10):337-40.
Prediction of steady-state plasma levels of amitriptyline and nortriptyline from a single dose 24 hr. level in depressed patients.

Brunswick DJ, Amsterdam J, Schless A, Rothbart M, Sandler K, Mendels J.

Amitriptyline and nortriptyline plasma levels were measured in depressed outpatients 24 hours after a single dose of amitriptyline and following chronic dosing to steady state. Plasma levels of amitriptyline and nortriptyline measured after the single dose correlated highly with steady state plasma levels. Full use as a test to rapidly place patients on a "therapeutic" dosage of drug will need to await a clear delineation of the relationship between blood levels and clinical response for amitriptyline.

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