Effects of Nonspecific Smooth Muscle Relaxants and Ca–Blocker on Ca–Release and Ca–Binding in Microsomal Fractions from Rabbit Taenia Coli

Abstract

A newly synthesized compound, BTM-1042 (cis(-)-2,3-dihydro-3-(4-methyl-piperazinyl)methyl-2-phenyl-1,5-benzothiazepin-4(5H)-one dihydrochloride) depressed the twitch responses of the ileum from guinea pig to electrical stimulation at 0.1 Hz. This inhibtory action of BTM-1042 was not influenced by naloxone, a narcotic antagonist. BTM-1042 proved to be almost as active as atropine on electrically stimulated ileum. BTM-1042 blocked muscarinic receptors but the potency was .apprx. one-thirteenth that of atropine. The responses of the ileum of guinea pig to nicotine and 5-hydroxytryptamine were inhibited by BTM-1042. BTM-1042 did not influence the release of transmitters from motor, sympathetic, nonadrenergic inhibitory (or purinergic nerve), noncholinergic excitatory nerves and responses of various smooth muscles mediated through drug receptors, except for the acetylcholine receptor. Spontaneous movement of the unanesthetized rabbit stomach was dose dependently depressed by BTM-1042 (0.04-0.2 mg/kg, i.v.). The potency ratio for BTM-1042 relative to atropine was 7.4. BTM-1042 is apparently a new type of potent, antispasmodic drug.