Studies on antihistaminic action. II: In vitro and in vivo effect of chlorpheniramine and its analogs on the uptake and retention of 5-hydroxytryptamine by rabbit blood platelets.

We have previously shown that the antihistaminic drug, chlorpheniramine maleate (CTM) increased blood histamine levels more rapidly than it did the blood 5-hydroxytryptamine (5-HT) levels in the rabbit (Sankar, Li and Santare, 1974). The present studies show that, while the in vitro addition of CTM to isolated rabbit blood platelets inhibited the platelet uptake of labeled 5-HT-14C, its administration to rabbits increased such in vitro uptake by platelets isolated from recipient animals. This is possibly due to the enhancement of release (depletion) of 5-HT from platelets in vivo. Such depleted platelets, will take up larger amounts of 5-HT on in vitro incubation. Our studies also show increased levels of blood 5-HT within minutes after administration of CTM to rabbits, further indicating that CTM deplets the platelets of their 5-HT on in vivo administration. Our present studies show that D-CTM is more active than brompheniramine in this system, while the fluorine derivative is least active. It is postulated that the antecedent release of histamine and 5-HT from tissues by antihistamines, renders further anaphylactic challenge or hypersensitivity episode less severe.