Abstract
The pharmacological actions of the optical isomers of cis-2, 3-dihydro-3- (4-methylpiperazinylmethyl) -2-phenyl-1, 5-benzothiazepin-4 (5H) -one (BTM) were studied and compared. Antiacetylcholine activity determined by the Magnus method was higher but antihistamine activity was lower with the (-) -compound than with the (+) -compound; the (±) -compound showed intermediate activities. The antiulcer action and antisecretory action in pylorus-ligated rats as well as the antistress ulcer action in mice were more potent with the (-) -compound than the (+) -compound. The optical isomers showed similar local anesthetic action, when tested by using the corneal reflex in guinea pigs. Analgesic action, tested by the acetic acid-induced writhing method, was observed with the (+) -compound, but not the (±) - or (-) -compound. The (+) -compound showed the strongest acute toxicity in mice, followed by the (±) - and the (-) -compounds in that order. These results suggest the presence of multiple targets for the various pharmacological activities. The (-) - compound appears to be more promising as an antiulcer agent, since the antiulcer effect was greater and the toxicity was milder as compared with (+) -compound.
