PHARMACODYNAMICS OF THE NEW H1-ANTAGONIST 3-AMINO-9,13B-DIHYDRO-1H-DIBENZ[C,F]IMIDAZO[1,5-A]AZEPINE HYDROCHLORIDE IN VOLUNTEERS

  • 1 May 1987
    • journal article
    • research article
    • Vol. 37-1  (5) , 569-572
Abstract
The inhibitory effects of 3-amino-9,13b-dihydro-1H-dibenz[c,flimidazo[1,5-a]azepine hydrochloride (WAL 801 CL)], a new H1-receptor antagonist, on histamine-induced skin wheals were studied in 9 volunteers. The study was a double-blind, randomized (Latin square) change-over intraindividual comparison of the effects of single doses of 2, 6 and 18 m WAL 801 CL and of placebo and 2 mg ketotifen on skin wheals induced by intradermal injections of 5 .mu.g hystamine 1, 2, 4, 6 and 8 h after administration of the drugs. The injection of 5 .mu.g was also made prior to each drug administration. The effects on psychological performance and the subjective state were also evaluated. The following tests were employed: simple visual reaction time (RT), critical flicker fusion frequency (C3F) and von Zerssen''s self-rating scale Bf-S, assessing state of mood. There was a washout period of at least 72 h between each course of treatment. A decrease in the size of the histamine wheal was observed 1 h after WAL 801 CL and was maintained for at least 8 h. The reduction in the size of the histamine wheal was between 44% (2.0 mg) and 71% (18.0 mg). After ketotifen a marked decrease in the wheal area was observed between 4 and 8 h after administration of the drug, with maximum histamine antagonism of 59% after 6 h. The inhibitory effects of 6 and 18 mg WAL 801 CL and 2 mg ketotifen were statistically significant compared with placebo. 8 of 9 subjects felt tired (subjective report) after ketotifen, corresponding changes could be detected by Zerssen''s state of mood scale Bf-S but not by other psychological performance measures (RT, C3F). Substantially lower and comparable with placebo incidence of side effects was observed after WAL 801 CL. There were no changes in psychological performance after any dose of WAL 801 CL. WAL 801 CL may be regarded as a clinically active H1-antagonist with no negative effects on the central nervous system.

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