Drugs online research references
Pharmacology. 1979;19(5):282-7.
Intraindividual similarity in the metabolism of amitriptyline and chlorimipramine in depressed patients.
Mellstrom B, Bertilsson L, Traskman L, Rollins D, Asberg M, Sjoqvist F.
The two structurally similar tricyclic antidepressant drugs amitriptyline (AT) and chlorimipramine (CI) were administered to 15 patients in a cross-over study. Approximately equimolar daily doses of the two drugs (5 mumol/kg body weight) were given as commercial tablets. Steady state plasma levels of the parent drugs and the demethyl metabolites were determined by high performance liquid chromatography. An about 5-fold interindividual variation was found in plasma levels of all four compounds. As the reciprocal plasma level during multiple dosing is proportional to the clearance of a compound, this parameter was used for linear regression analysis. In the 15 patients there was a significant correlation between the reciprocal plasma levels of CI and its metabolite demethylchlorimipramine (r = 0.76; p less than 0.001) and also between AT and its metabolite nortriptyline (r = 0.52; p less than 0.05). The reciprocal plasma levels of the parent compounds AT and CI were closely correlated (r = 0.87; p less than 0.001). A similar correlation was found for the demethyl metabolites (r = 0.77; p less than 0.001). The results indicate that similar factors control the plasma levels of AT and CI during treatment and that similar enzymes may be involved in the metabolism of the two drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=538083&dopt=Abstract
Therapie. 1965 May-Jun;20(3):759-69.
[Contribution to the study in animals of the psychotropic activity of imipramine, amitriptyline and their monodemethylated derivatives]
[Article in French]
Boissier JR, Simon P, Fichelle-Pagny J, Lwoff JM.
PMID: 5840886
J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):83-9.
Experimental amitriptyline intoxication: electrophysiologic manifestations and management.
Nattel S, Keable H, Sasyniuk BI.
Amitriptyline intoxication can result in severe ventricular arrhythmias that may be refractory to medical management. The mechanisms of these arrhythmias are unclear, and their optimal management is problematic. We studied the cardiac effects of amitriptyline infusion in anesthetized and awake dogs. Amitriptyline significantly increased heart rate, QRS duration, and AH and HV intervals. The concentration-response curves for these effects were, however, quite different, with significant changes beginning at a concentration of 1.5 +/- 0.4 mg/L for heart rate, compared with 2.4 +/- 0.4 mg/L for QRS and HV intervals and 3.7 +/- 0.5 mg/L for the AH interval. Ventricular tachyarrhythmias developed after marked QRS widening had occurred, and appeared in all six awake dogs and five of the six anesthetized dogs studied. Sodium bicarbonate was given to seven animals with ventricular tachyarrhythmias, and it rapidly reversed the arrhythmia in all instances. The benefit from sodium bicarbonate could not be attributed to changes in serum potassium or amitriptyline concentrations. It may have been due to alkalinization or changes in serum sodium concentration. These experiments suggest that: (a) amitriptyline intoxication frequently produces ventricular tachyarrhythmias, if high enough drug concentrations are achieved; (b) these arrhythmias are associated with marked slowing of intraventricular conduction; and (c) sodium bicarbonate is effective therapy for amitriptyline-induced ventricular arrhythmia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6199617&dopt=Abstract
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