Pharmacology of the new H1-receptor antagonist setastine hydrochloride.

Abstract

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.

• Authors: J Porszász, F Varga, K G Porszász, J Szolscányi, L Barthó, L Petöcz, L Kápolnai
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 40 Issue 12 Pg. 1340-5 (Dec 1990) ISSN: 0004-4172 [Print] Germany
• PMID: 1982751 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Azepines
• Central Nervous System Depressants
• Histamine H1 Antagonists
• Parasympatholytics
• Serotonin Antagonists
• setastine
• Histamine
• Clemastine
• Pyrilamine

Topics

• Animals
• Azepines (pharmacology)
• Behavior, Animal (drug effects)
• Binding, Competitive (drug effects)
• Bronchi (drug effects)
• Capillary Permeability (drug effects)
• Cats
• Central Nervous System Depressants (pharmacology)
• Clemastine (pharmacology)
• Female
• Gastric Acid (metabolism)
• Guinea Pigs
• Hemodynamics (drug effects)
• Histamine (toxicity)
• Histamine H1 Antagonists (pharmacology)
• In Vitro Techniques
• Male
• Mice
• Muscle Contraction (drug effects)
• Muscle, Smooth (drug effects)
• Parasympatholytics
• Passive Cutaneous Anaphylaxis (drug effects)
• Pyrilamine (metabolism)
• Rats
• Serotonin Antagonists