Lack of interaction between tricyclic antidepressants and clonidine at the alpha 2-adrenoceptor on human platelets.

The pharmacologic interaction between tricyclic antidepressants and clonidine at the alpha 2-adrenoceptor was examined in human platelets by quantifying the ability of tricyclic antidepressant drugs to inhibit clonidine-stimulated platelet aggregation in vitro. Platelet aggregation induced by increasing concentrations of clonidine (0.3 to 3 microM) was not altered by pretreatment of the platelets with 10 microM imipramine. Imipramine at concentrations above 100 microM attenuated clonidine-induced platelet aggregation, but this was a nonspecific drug effect because the high concentrations of imipramine inhibited adenosine diphosphate-induced platelet aggregation as well. Desmethyldoxepin and nortriptyline also inhibited platelet aggregation nonspecifically at higher concentrations (greater than 10 microM). We were also not able to establish a specific interaction between alpha-methlnorepinephrine (the active metabolite of methyldopa) and the tricyclic antidepressants at the platelet alpha 2-adrenoceptor. Our data suggest that if there is an adverse dynamic interaction between tricyclic antidepressants and clonidine, the interaction occurs at a site other than the alpha 2-adrenoceptor.