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Tri cyclic anti depressants as anti muscarinic drugs in vivo and in vitro studies

, : Tri cyclic anti depressants as anti muscarinic drugs in vivo and in vitro studies. Biochemical Pharmacology 26(17): 1559-1568

Antagonistic activity of nortriptyline, amitriptyline and imipramine to the hypothermic and tremorigenic activity of oxotremorine was determined in mice. The peripheral anticholinergic relative potencies of these drugs were evaluated by following dose-dependent time profiles of their mydriatic activity. Binding constants of the antidepressant agent toward the central muscarinic receptor from the mouse whole brain homogenate were determined in vitro and could be correlated with ED50 values found for the 3 drugs' in vivo responses. The 3 antidepressants tested were found to be 100-fold less active than scopolamine.cntdot.HBr in all 4 biological preparations selected. Their anticholinesterase activity towards the enzyme in whole mouse brain homogenate apparently was too low to make any possible contribution to their activity in vivo. Relationships between structure and function and the possible contribution of their antimuscarinic property to the observed in vivo effects are discussed.

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Accession: 006839947

PMID: 901576

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