Pharmacology of the new H1-receptor antagonist setastine hydrochloride.

Setastine HCl (N-(1-phenyl-1-[4-chlorophenyl])-etoxy-ethylene-perhydroazepine hydrochloride, Loderix; CAS 64294-95-7) is a potent antagonist of histamine H1-receptor mediated responses. The antihistamine activity of the compound is similar to that of clemastine fumarate in the following assays: histamine-induced lethality and bronchospasm in guinea-pigs, plasma extravasation in rats, and contractile action in isolated guinea-pig ileum. Setastine HCl inhibits anaphylactic shock in guinea-pigs sensitized by horse serum. No antiserotonin, anticholinergic and antiadrenergic effect of the compound can be detected. Setastine HCl has a long lasting (up to 16 h) antihistamine effect with a good oral effectiveness. It shows no cardiovascular effects in cats. Setastine HCl shows a much weaker CNS depressant activity than clemestine fumarate measuring inhibition of amphetamine-induced hypermotility, rotarod performance, potentiation of ethanol-narcosis in mice, and prolongation of hexobarbital sleeping time in rats. In displacement studies (3H-mepyramine) setastine HCl had significantly weaker affinity for the central nervous system (CNS) H1-receptors than clemastine fumarate. It is concluded that setastine HCl is a non-sedative highly active H1-antagonist.