In vitro and in vivo studies of the non-sedating antihistamine epinastine

Arzneimittelforschung. 1988 Oct;38(10):1446-53.

Abstract

Epinastine (3-amino-9,13b-dihydro-1H-dibenz [c,f]imidazo[1,5-a]azepine hydrochloride, WAL 801 CL) was tested in vitro and in vivo in comparison with other H1-receptor antagonists. In the guinea pig ileum and in receptor binding studies the test substance showed a high affinity to H1-receptors. The following rank order was determined: WAL 801 CL greater than astemizole greater than terfenadine. These results were confirmed in vivo. The studies were carried out with oral and intravenous administration of WAL 801 CL to assess the inhibition of histamine-induced reactions in the skin or the lung of rats, dogs and guinea pigs. 10- to 100fold antihistaminic doses of WAL 801 CL showed no effect on the sleeping-waking behaviour of cats. From this and other results it is suggested that the compound does not penetrate in the central nervous system. The action pattern of WAL 801 CL as a non-sedating antihistamine corresponds more to that of terfenadine than that of ketotifen.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Astemizole
  • Benzhydryl Compounds / metabolism
  • Benzhydryl Compounds / pharmacology
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology
  • Cats
  • Dibenzazepines / metabolism
  • Dibenzazepines / pharmacology*
  • Dogs
  • Female
  • Guinea Pigs
  • Histamine H1 Antagonists / metabolism
  • Histamine H1 Antagonists / pharmacology*
  • Histamine Release / drug effects
  • Ileum / drug effects
  • Imidazoles*
  • In Vitro Techniques
  • Ketotifen / pharmacology
  • Male
  • Promethazine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Histamine H1 / metabolism
  • Sleep / drug effects
  • Terfenadine
  • Wakefulness / drug effects

Substances

  • Benzhydryl Compounds
  • Benzimidazoles
  • Dibenzazepines
  • Histamine H1 Antagonists
  • Imidazoles
  • Receptors, Histamine H1
  • Terfenadine
  • Astemizole
  • Promethazine
  • epinastine
  • Ketotifen