Chemicopharmacological studies on antispasmodic action,pt.18

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  • Chemicopharmacological Studies on Antispasmodic Action. XVIII. On the Antibarium Action of Papaverine-like Antispasmodics tested on Plexus-free Circular Muscle and Innervated Longitudinal Muscle.

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It was concluded from the foregoing experiments through Magnus method (at 26°and 38°) with (1) excised intact intestines of mice and guinea pigs, (2) longitudinal strip, (3) longitudinal muscle strip with ganglion and circular muscle, (4) longitudinal muscle strip without circular muscle, (5) circular muscle strip with ganglion and longitudinal muscle, and (6) circular muscle strip (without ganglion cells) of cat small intestine, and (7) tracheal strip preparation of guinea pig that : (1) Ba2+ had almost similar activity on different kinds of smooth muscle preparations, in quality of contraction and in effective concentration. Ganglion-blocking agents inhibited Ba2+-contraction of the ileum preparation, and the antagonism was competitive, but they antagonized nicotine in 1/100 or lower concentration on all the ileum preparations. Therefore, Ba2+-must have a site of action other than that of nicotine and the ganglion blocking agents combine with barium-receptor and nicotine-receptor, each with different affinity. It is very probable that the barium-receptor is present on smooth muscle of small intestine and the ganglioplegics can combine with it and that the ganglionic action of Ba2+ cannot be revealed. (2) Antagonism between Ba2+ and strongly basic antispasmodics (pKa>8.5) of II-group was competitive and that between Ba2+ and papaverine of I-group, which would exert through some physicochemical property of non-ionized molecules, was non-competitive on all the smooth muscle preparations used. (3) Since the antibarium action is qualitatively different between I-group and II-group antispasmodics, the comparison of the potency ratio to papaverine as standard must be made under careful consideration. (4) ACh and atropine-like antispasmodics were proved to have higher potency on intact ileum and longitudinal muscle strip than on circular muscle strip with and without ganglion cells. (5) Atropine inhibited the nicotine-contraction of guinea pig ileum non-competitively in 1000 times or higher concentration than that at which atropine competitively antagonizes the contraction by ACh.

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