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Anticholinergic activity in the serum of patients receiving maintenance amitriptyline or doxepin therapy.
Acta Pharmacologica et Toxicologica 1985 January
The anticholinergic activity in serum of depressive patients receiving amitriptyline (50-300 mg/day) or doxepin (50-225 mg/day) was measured using a radioreceptor assay. In this method the membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist, quinuclidinyl benzilate. Using atropine as a standard, the antimuscarinic activity of several compounds can be measured in the serum of patients receiving drugs with anticholinergic effects or side-effects. The steady state serum levels of amitriptyline and doxepin and their desmethylated metabolites, nortriptyline and desmethyldoxepin were measured by radioimmunoassay in the same serum samples. The antimuscarinic activity in serum measured as atropine equivalents was 2.7 +/- 0.4 (S.E.M.) ng/ml in amitriptyline patients and 1.1 +/- 0.2 ng/ml in doxepin patients. There was a highly significant correlation (P less than 0.001) between amitriptyline (r = 0.92) and nortriptyline (r = 0.79) concentrations and serum antimuscarinic activity. The correlation was less clear, although statistically significant for doxepin (r = 0.42, P less than 0.05) and desmethyldoxepin (r = 0.58, P less than 0.01). The better correlation between serum drug levels and antimuscarinic activity in amitriptyline than in doxepin patients is probably due to the higher affinity of amitriptyline and its desmethylated metabolite to muscarinic receptors with the doses used in the present study. The method may have clinical applications e.g. in evaluation of excessive anticholinergic activity in patients.
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