Comparison of pharmacological properties of optical isomers and a racemic mixture of epinastine.
Some pharmacological effects of d- and l-isomers of epinastine (WAL 801 CL, 3-amino-9,13b-dihydro-1H-dibenz [c,f]imidazo[1,5-a]azepine hydrochloride; CAS 80012-43-7) were studied in comparison with that of dl-epinastine. Although no significant difference was detected, d-epinastine is slightly more active than the l-isomer in the depressant actions of the central nervous system. However, in EEG power spectra recorded at the frontal cortex, occipital cortex, hippocampus and amygdala in conscious rats, no appreciable differences were recognized between two optical isomers and a racemic mixture. Furthermore, the extents of compound 48/80-induced lethality, antagonism on histamine-induced contraction of guinea pig ileum and histamine release from rat peritoneal mast cells were almost the same among the racemate and optical isomers of epinastine. In addition, two stereoisomers caused an almost equal degree of inhibition in antigen-induced histamine release from the lung pieces of sensitized guinea-pigs and the equivalent level of inhibition was exerted by the racemate.
Tasaka
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Kamei
C
C
Izushi
K
K
Tsujimoto
S
S
Yoshida
T
T
D000818:Animals; D003984:Dibenzazepines / Q000494:pharmacology*; D004569:Electroencephalography; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects; D013237:Stereoisomerism; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; C053090:epinastine