Ann Clin Biochem. 1978 Jul;15(4):221-5.
Radioimmunoassay of amitriptyline and nortriptyline in body fluids.

Mould GP, Stout G, Aherne GW, Marks V.

A radioimmunoassay for the measurement of amitriptyline and nortriptyline in serum, saliva, and urine is described. The sensitivity of the assay is such that 0.5 ng/ml of drug can be measured, although the assay does not distinguish between amitriptyline and nortriptyline. Other tricyclic compounds cross-react with the antiserum to varying degrees, but the metabolites of amitriptyline did not significantly cross-react. Total tricyclic compounds were detected in serum and saliva after single oral doses of amitriptyline, although the absorption was slow.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=567954&dopt=Abstract Elavil amitriptyline




Agents Actions. 1990 Apr;30(1-2):41-3.
The activity of amitriptyline as a differential inhibitor of amine secretion from rat peritoneal mast cells: the contribution of amine uptake.

Purcell WM, Hanahoe TH.

Hatfield Polytechnic, Herts, UK.

Amitriptyline, at a concentration of 10(-4) M, significantly inhibited the release of histamine from purified peritoneal rat mast cells in response to compound 48/80, but was without effect upon the output of 5-HT. The reduction was not extensive, and concentrations of the drug above or below 10(-4) M were without effect. Amitriptyline (10(-8)-10(-4) M) inhibited uptake of exogenous 5-HT in a concentration dependent manner. Paradoxically, however, histamine uptake was significantly increased in the presence of this drug, but only at a concentration of 10(-4) M. This effect was observed at 4 degrees C for both amines. Concentrations of amitriptyline in excess of 10(-4) M caused lysis of the mast cells. These results suggest that the observed selective inhibitory effect of amitriptyline upon histamine output may be a function of altered amine uptake rather than differential inhibition and 5-HT secretion.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1695456&dopt=Abstract Elavil amitriptyline




J Cardiovasc Pharmacol. 1990 Nov;16(5):693-701.
Comparative effects of antidepressants, amitriptyline, and maprotiline on intraventricular conduction, effective refractory period, and incidence of ventricular arrhythmias induced by programmed stimulation in dog hearts after myocardial infarction.

Hashimoto H, Nishimoto M, Ozaki T, Oohara K, Nakashima M.

Department of Pharmacology, Hamamatsu University School of Medicine, Japan.

The effects of amitriptyline and maprotiline, standard tricyclic and tetracyclic antidepressants, on intraventricular conduction, the effective refractory period (ERP), and the incidence of ventricular arrhythmias induced by programmed stimulation were studied and compared in dog hearts after myocardial infarction. Amitriptyline at doses of 1-3 mg/kg significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and dose-dependent manner. Amitriptyline at doses of 2 and 3 mg/kg slowed conduction slightly in normal zones. The ERP was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Maprotiline at doses of 1-3 mg/kg slowed conduction in infarcted zones to a lesser extent as compared with amitriptyline, although severely depressed conduction in the infarcted zone was obviously slowed by maprotiline. Maprotiline did not increase the incidence of ventricular arrhythmias significantly. From the present results, maprotiline appears to have less cardiac toxicity than amitriptyline, although maprotiline produces a slight decrease in conduction of infarcted zones.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1703589&dopt=Abstract Elavil amitriptyline




In Vitro Cell Dev Biol. 1991 Dec;27A(12):921-6.
A primary culture system of adult rat heart cells for the study of toxicologic agents.

Welder AA, Grant R, Bradlaw J, Acosta D.

College of Pharmacy, University of Oklahoma Health Sciences Center, Division of Medicinal Chemistry and Pharmacodynamics, Oklahoma City 73190.

Tricyclic antidepressants (TCAs) are currently used in the treatment of mental depression and nocturnal enuresis. Clinically, these drugs are useful; however, cardiotoxicity can occur even with therapeutic dosages. For example, TCAs are known to alter myocardial function, induce arrhythmias, and produce heart block in individuals with a normal cardiovascular history. The present study was undertaken to establish a culture system of spontaneously contracting adult primary myocardial cells for toxicologic testing and to examine their contractility, morphology, and lactate dehydrogenase release (LDH) after treatment with one of the most cardiotoxic TCAs, amitriptyline. Primary myocardial cell cultures were obtained from approximately 60- to 90-day-old Sprague-Dawley rats. After the cells had been grown in culture for 11 days, they were treated with amitriptyline (1 x 10(-3), 1 x 10(-4), and 1 x 10(-5) M) for 2 to 24 h. The highest concentration of amitriptyline (1 x 10(-3) M) completely destroyed the cardiac muscle cells. In addition to moderate and severe vacuole, granule, and pseudopodia formation, all contractile activity was inhibited as early as 2 h after exposure to the intermediate concentration of 1 x 10(-4) M amitriptyline. Significant LDH release did not occur until 8 h after treatment with this intermediate concentration. Even though there was no significant LDH release at all 3 time points tested, there was a 50% decrease in beating activity (154 +/- 9 to 77 +/- 5 beats/min) and initiation of vacuole formation by 2 h with the lowest concentration of amitriptyline (1 x 10(-5) M). This study presents a new apparatus for the isolation of adult cardiac myocytes for the establishment of primary cell cultures for toxicologic testing. Furthermore, these data demonstrate that amitriptyline induces a concentration- and time-dependent cardiotoxic profile in a model of spontaneously contracting adult cardiac muscle cells in culture.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1757397&dopt=Abstract Elavil amitriptyline




Pol J Pharmacol Pharm. 1991 Jan-Feb;43(1):27-32.
The effect of some microsomal enzyme inducers on amitriptyline distribution in rats.

Negrusz A, Brandys J, Piekoszewski W.

Department of Toxicology Medical Academy in Krakow, Poland.

The influence of different types of enzyme inducers: phenobarbital, Aroclor 1254 and benzo(a)pyrene, on distribution of amitriptyline and its metabolite nortriptyline in rats was investigated. The level of amitriptyline and nortriptyline in serum, brain, heart and liver was determined by gas chromatography. The maximum concentration values of amitriptyline and nortriptyline as well as areas under concentration-time curves (AUC0-6) in serum and organs were statistically compared using Student t test and AUCCOMP computer program. The results suggest that studied xenobiotics significantly influence the distribution of amitriptyline and nortriptyline in rats. The changes of these drugs concentration in target organs may be very important from the toxicological point of view.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1771161&dopt=Abstract Elavil amitriptyline




Zhonghua Shen Jing Jing Shen Ke Za Zhi. 1991 Apr;24(2):68-70, 123.
[A control study of clomipramine and amitriptyline for treating obsessive-compulsive disorder]

[Article in Chinese]

Zhao JP.

Mental Health Institute of Hunan Medical University, Changsha.

This paper reported a comparative study of clomipramine (n = 21) and amitriptyline (n = 18) for treatment OCD. The improvement rate of clomipramine and amitriptyline was 95.2% and 55.6%, respectively (P less than 0.01). The decreased scores of obsessive-compulsive and depressive factors of SCL-90 of clomipramine were higher than amitriptyline. The results showed that clomipramine has better therapeutic effects and less side-effects than amitriptyline.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1860383&dopt=Abstract Elavil amitriptyline




J Chromatogr. 1976 Mar 3;118(1):65-74.
Determination of plasma amitriptyline by electron-capture gas chromatography after oxidation to anthraquinone.

Hartvig P, Strandberg S, Naslund B.

A selective procedure is described for the determination of amitriptyline in plasma. The method involves extraction, separation of amitriptyline from its metabolites and subsequent oxidation by ceric sulphate in 5.4 M sulphuric acid. The oxidation product, anthraquinone, is determined by means of electron-capture gas chromatography. The metabolites were separated by a column chromatographic extraction technique. The choice of oxidation reagent, optimum conditions for the oxidation, and the electron-capture properties of anthraquinone are discussed. The method can be used to determine down to 2 ng of amitriptyline in a plasma sample; the relative standard deviation at the 50-ng level was 4.0% (n = 8). The levels of amitriptyline found in a series of plasma samples are compared with those obtained by gas chromatography with use of nitrogen-specific detection; the two techniques gave coincident results.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1249173&dopt=Abstract Elavil amitriptyline