Neuropsychobiology. 1984;12(1):9-15.
Serum levels and response to amitriptyline in depressed out-patients.

Rowan PR, Paykel ES, Marks V, Mould G, Bhat A.

Serum levels of amitriptyline plus nortriptyline were measured by radioimmunoassay at 1 and 6 weeks in depressed out-patients treated with amitriptyline for 6 weeks. Serum concentrations at 6 weeks were higher in older patients. Serum levels showed no relationship to clinical response at 6 weeks, and a week inverse relationship with response at 2 weeks. Routine monitoring of serum levels appears to be of little value in depressed out-patients treated with amitriptyline.

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Psychopharmacology (Berl). 1982;77(3):236-41.
Blood noradrenaline and 5-HT levels in depressed women during amitriptyline or lithium treatment.

Corona GL, Cucchi ML, Santagostino G, Frattini P, Zerbi F, Fenoglio L, Savoldi F.

Noradrenaline levels and platelet and free serotonin concentrations were studied in depressed women in-patients (n=78) before and during amitriptyline (n=41) or lithium treatment (n=37). Pronounced monthly differences in platelet serotonin level have been shown in these subjects before treatment. In all clinical subgroups (neurotic, involutional, manic-depressive patients) a significant fall in platelet serotonin level was observed with amitriptyline medication while an increase was noted with lithium. No significant correlations between serotonin concentrations and clinical outcome were found. Amitriptyline treatment also produced a decrease in peripheral noradrenaline concentration in all subgroups, while an increase was observed with lithium. Some correlations between noradrenaline level and degree of depression were noted in patients treated with amitriptyline or lithium. A more extended analysis of blood amine levels could supply meaningful information on the peripheral action of antidepressive drugs on noradrenaline and serotonin concentrations in depression.

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Clin Pharmacol Ther. 1983 Mar;33(3):360-6.
Amitriptyline disposition in young and elderly normal men.

Schulz P, Turner-Tamiyasu K, Smith G, Giacomini KM, Blaschke TF.

The disposition of a single parenteral or single oral dose of amitriptyline was followed in seven young (mean age 22 yr, range 21 to 23) and five elderly (mean age 71 yr, range 62 to 81) healthy men. The mean systemic clearance did not change with age (10.8 +/- 2.1 ml/min/kg in elderly and 12.5 +/- 2.3 ml/min/kg in young subjects). Mean t 1/2 was longer in the older (21.7 +/- 2.9 hr) than in the younger group (16.2 +/- 6.1 hr) as a result of an increase in the volume of distribution (17.1 +/- 2.4 and 14.1 +/- 2.0 l/kg). The bioavailability and the fraction of the drug bound to plasma proteins did not change with age. Single doses of amitriptyline were not well tolerated clinically by either elderly or young subjects, which confirms the need for a gradual buildup in the therapeutic regimen and for close clinical surveillance of elderly depressed patients treated with amitriptyline.

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Can J Physiol Pharmacol. 1982 Feb;60(2):193-200.
The effect of amitriptyline, mianserin, and viloxazine at pre- and post-junctional muscarinic receptors in guinea-pig ileal longitudinal muscle.

Kwok YH, Mitchelson F.

The antimuscarinic activity of amitriptyline, mianserin, and viloxazine was compared with atropine in guinea-pig ileal longitudinal muscle. The pA2 values obtained using carbachol (CCh) as agonist were as follows: atropine, 9.55; amitriptyline, 7.50; mianserin, 6.40; and viloxazine, 4.91. Responses to transmural electrical stimulation (1-50 Hz) were more resistant than those produced by CCh to inhibition by atropine and the antidepressants. This did not appear to be due to a selective inhibition of prejunctional inhibitory muscarinic receptors, as a pA2 of 8.73 was obtained with atropine for the depression of oxotremorine-induced inhibition of acetylcholine (ACh) output. Amitriptyline (10 micrometers) caused a 2.4-fold increase in ACh output and was 200-fold weaker than atropine at doubling ACh output in the longitudinal muscle stimulated at 0.3 Hz. Mianserin (10 micrometers) and viloxazine (1-10 micrometers) did not significantly affect ACh output. It is suggested that the antidepressants exhibits a greater affinity for the postjunctional muscarinic receptors in the guinea-pig ileal longitudinal muscle.

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Eur J Pharmacol. 1978 Oct 1;51(3):193-8.
The antiarrhythmic action of amitriptyline on arrhythmias associated with myocardial infarction in dogs.

Wilkerson RD, Sanders PW.

The antiarrhythmic activity of amitriptyline, a tricyclic antidepressant, was evaluated in anesthetized dogs 24 h after coronary occlusion, during the period of spontaneous ventricular arrhythmias. In all experiments amitriptyline was administered i.v. in incremental doses of 0.3 mg/kg at 1 min intervals until a conversion to normal sinus rhythm was evident. Amitriptyline administration resulted in conversion of the ventricular arrhythmia to a normal sinus rhythm in 100% of the animals tested at a mean dose of 1.3 +/- 0.1 mg/kg. Smaller doses also resulted in a dose-related decrease in non-sinus nodal pacemaker activity. Lidocaine, when administered to the same group of animals, produced a reduction of ectopic pacemaker activity, but did not eliminate it at a cumulative dose of 2 mg/kg. Antiarrhythmic doses of amitriptyline did not produce significant changes in arterial blood pressure, cardiac output or electrocardiographic parameters associated with atrioventricular or intraventricular conduction. The results of this study suggest that at very low doses amitriptyline may be an effective antiarrhythmic agent in ventricular arrhythmias associated with myocardial ischemia.

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Pharmacopsychiatria. 1982 Nov;15(6):197-204.
Mianserin and maprotiline as compared to amitriptyline in severe endogenous depression. A new methodological approach to the clinical evaluation of the efficacy of antidepressants.

Cording-Tommel C, von Zerssen D.

Present methodological problems in assessing the clinical efficacy of putative antidepressants require testing of various new strategies. The approach presented by the authors allows "natural" clinical treatments to be evaluated scientifically; double-blind conditions are replaced by other measures of bias control. In this paper, the clinical effectiveness of mianserin in homogenous groups of inpatients with severe endogenous depression is compared with that of maprotiline and amitriptyline. The frequency of change of the respective antidepressant by the physicians in charge as well as patients' self-evaluations based on v. Zerssen's Mood Scale served as outcome criteria. No difference in efficacy was found between maprotiline and amitriptyline, whereas mianserin was significantly less effective. The number of patients complaining of side effects from the two tetracyclic compounds was no less than in the case of amitriptyline. There were, however, qualitative differences; with maprotiline, myoclonic jerks were observed in some cases. The hypothesis that mianserin may possess sedative-anxiolytic rather than antidepressive properties is discussed in conjunction with methodological and theoretical implications.

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Res Commun Chem Pathol Pharmacol. 1981 Sep;33(3):537-45.
Tricyclic antidepressants: a simplified approach for the routine clinical monitoring of parent drug and metabolites in plasma using HPLC.

Dixon R, Marin D.

A simplified procedure for the routine clinical monitoring of amitriptyline, nortriptyline, imipramine and their metabolites in plasma using high performance liquid-chromatography (HPLC) has been developed. Commonly encountered problems in the analyses of tricyclic antidepressants such as low recovery, adsorption to glass and extensive "clean-up" procedures have been avoided by judicious choice of solvents, extraction procedures and chromatographic technique. The method involves a single extraction of 1 ml of plasma at pH 10.5 with iso-octane:methyl t-butyl ether (9:1) in a disposable polypropylene tube, solvent transfer to and evaporation in a similar tube followed by direct HPLC of the extract on a 10 micrometer silica gel column using methanol containing 0.1% concentrated ammonium hydroxide as the mobile phase and detection at 254 nm. Good chromatographic separation of amitriptyline (AT), 10-hydroxy-amitriptyline (10-OH-AT), nortriptyline of amitriptyline (NT), 10-hydroxy-nortriptyline (10-OH-NT), imipramine (IM) and desmethyl-imipramine (DMI) is achieved. IM is used as an internal standard for the analysis of plasma samples from patients receiving AT and NT, while NT is used as the internal standard for analysis of IM and its metabolite DMI. Overall recoveries exceed 80% and the limits of sensitivity are about 25 ng/ml for each compound quantitated. Although the utility of the method is illustrated in the analysis of a selection of plasma samples from patients receiving various therapeutic doses of AT, NT and IM, it would appear that the procedure offers a simplified approach for the analysis of other tricyclic antidepressants in a clinical setting.

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