Different effects of centrally acting drugs on rabbit platelet aggregation: with special reference to selective...

Twenty-four drugs, consisting of antipsychotics, tricyclic antidepressants, other centrally acting drugs, and related compounds, were studied for their effects on aggregation of rabbit platelets. Phenothiazine neuroleptics, haloperidol, sultopride, tricyclic antidepressants, sulpiride, atropine, and propranolol showed a selective inhibitory effect on the collagen-induced aggregation, but not on aggregations induced by arachidonic acid (AA) or adenosine diphosphate (ADP). These drugs are thought to inhibit the liberation of AA from phospholipids in platelet membranes, suggesting that they might inhibit phospholipases. Mepyramine, promethazine, phentolamine, and clozapine inhibited the aggregations evoked by collagen and AA, but failed to inhibit the ADP-induced aggregation. These drugs might inhibit the generation of prostaglandin endoperoxides or thromboxanes. Phenobarbital, phenytoin, procaine, lidocaine, flurazepam, trihexyphenydil, and lithium carbonate did not inhibit any kind of aggregation at the concentrations used. The clinical and pharmacological significance of these findings is discussed; it seems that the inhibitory effects of antipsychotics and antidepressants on platelet aggregation are closely related to the specific clinical and psychotropic effects of these drugs, but not to other actions.