Pharmacological characterisation of the smooth muscle antispasmodic agent tiropramide.
(+/-) Tiropramide hydrochloride, its D and L optical isomers and some of its metabolites were characterized in a number of in vitro pharmacological tests. Tiropramide showed broad spectrum antispasmodic activities on the isolated stomach of guinea pig electrically stimulated; on the longitudinal muscles of the ileum of guinea pig stimulated by electrical impulses, BaCl2, acetylcholine, histamine, serotonin, substance P and cholecystokinin octapeptide (CCK-8); on the spontaneous contractions and on the electrical inhibition of the jejunum of rabbit; on the spontaneous contractions and on the contractions provoked by BaCl2 and acetylcholine of the ascending colon of the rat; on the contractions provoked by BaCl2, acetylcholine, histamine and cerulein of the circular muscles of the gall bladder of the guinea pig; on the spontaneous contractions of the pyel-ureter preparation of the guinea pig; on the contractions of the uterus of the rat provoked by oxitocin, serotonin, acetylcholine, PGF2; on the spontaneous contraction of the portal vein of the rat; on the constriction of the tail artery of the rat provoked by electrical stimulation, epinephrine and ergotamine; on the contractions of the aortic strip of the rabbit stimulated by norepinephrine; on the contractions of the strip of bovine coronary artery depolarized by HCl. In general tiropramide had antispasmodic effect at 5-60 mumol/l concentration. It was more potent than papaverine on contractions provoked by electrical or chemical stimuli, and was less potent or ineffective on spontaneous and "physiological" contractions of the different smooth muscle preparations. Tiropramide had small effects on vascular smooth muscles and showed very small calcium channel blocking activity.
Setnikar
I
I
Rotta Research Laboratorium S.p.A., Monza.
Cereda
R
R
Pacini
M A
MA
Revel
L
L
Makovec
F
F
D000818:Animals; D002417:Cattle; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007536:Isomerism; D007583:Jejunum / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010276:Parasympatholytics / Q000097:blood / Q000494:pharmacology*; D011169:Portal Vein / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000097:blood / Q000494:pharmacology / Q000031:analogs & derivatives; D001743:Urinary Bladder / Q000187:drug effects; D014599:Uterus / Q000187:drug effects
D010276:Parasympatholytics; D014443:Tyrosine; C031173:tiropramide