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.
D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000929:Antidepressive Agents, Tricyclic; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine