Pharmacodynamics of the new H1-antagonist 3-amino-9,13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine hydrochloride in volunteers.
The inhibitory effects of 3-amino-9,13b-dihydro-1H-dibenz[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 mg WAL 801 CL and of placebo and 2 mg ketotifen on skin wheals induced by intradermal injections of 5 micrograms hystamine 1, 2, 4, 6 and 8 h after administration of the drugs. The injection of 5 micrograms 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).(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001381:Azepines / Q000494:pharmacology*; D003984:Dibenzazepines; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D005425:Flicker Fusion / Q000187:drug effects; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012882:Skin Tests
D001381:Azepines; D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D006632:Histamine; C053090:epinastine; D007665:Ketotifen