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.
Porszász
J
J
Department of Pharmacology, Medical School, Pécs, Hungary.
Varga
F
F
Porszász
K G
KG
Szolscányi
J
J
Barthó
L
L
Petöcz
L
L
Kápolnai
L
L
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002974:Clemastine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000633:toxicity; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D012702:Serotonin Antagonists
D001381:Azepines; D002492:Central Nervous System Depressants; D006634:Histamine H1 Antagonists; D010276:Parasympatholytics; D012702:Serotonin Antagonists; C053758:setastine; D006632:Histamine; D002974:Clemastine; D011738:Pyrilamine