Lack of interaction between tricyclic antidepressants and clonidine at the alpha₂-adrenoceptor on human platelets

The pharmacologic interaction between tricyclic antidepressants and clonidine at the alpha₂-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 (0.1 to 3μM) was not altered by pretreatment of the platelets with 10 μM imipramine. Imipramine at concentrations above 100 μM 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 (>10 μM). We were also not able to establish a specific interaction between alpha- methylnorepinephrine (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 alpha₂-adrenoceptor.