Biological activities of novel thienothiazine derivatives on heart and smooth muscle preparations of guinea pigs

New thienothiazine derivatives which differ in their side chains on the nit rogen atom of the thienothiazine ring were investigated regarding their bio logical activity and compared with calcium antagonistic drugs. Isometric co ntraction force was measured in guinea-pig papillary muscles, aortic strips and terminal ilea. Chronotropic activity was studied in right atria guinea pigs. MS 69 with a ethylpyridylcarbonyl side chain had the most potent neg ative inotropic effect on isolated papillary muscles, followed by MS 74, wh ich has an ethylmethylpiperazinylthiocarbonyl side chain. The negative inot ropic effect could be antagonized by increasing the extracellular calcium c oncentration. MS 87 with an ethylpyridylcarboxamide side chain had the most potent relaxing effect on aortic strips and MS 48 with an ethylbenzylpiper azinyl-carbonyl side chain was most potent on terminal ilea. Compounds with a more hydrophilic side chain had less activity. It is concluded that incr easing the lipophilicity by substitution of an oxygen atom by a sulfur atom (MS 74) or addition of a pyridine ring (MS 69) results in a higher biologi cal activity.