Effect of fedotozine on human distal colon.
Fedotozine was rested in colonic strips removed during surgery from patients suffering from different diseases of the colon; the effects were compared to those of morphine and of the selective opiate agonist U-69593. Fedotozine did not affect the spontaneous motility of human colonic strips, unless very high concentrations were used. Fedotozine (10(-6)-3 x 10(-4) M) induced a concentration-dependent reduction of the excitatory effect induced by field stimulation, an effect which was partially mimicked by compound U-69593 and by morphine but not inhibited by naloxone. The cumulative dose-response curve to exogenous acetylcholine was inhibited by fedotozine (3 x 10(-4) M), whereas morphine had no effect up to 3 x 10(-4) M. In colonic strips incubated with [3H]-choline, fedotozine (10(-5)-10(-4) M) induced an erratic decrease of acetylcholine-release induced by electric stimulation. In our experimental model, the inhibitory effect of fedotozine does not seem to be related to opioid receptor activation.
Adami
M
M
Istituto di Farmacologia, Università di Parma, Italy.
Bertaccini
G
G
Roncoroni
L
L
Cobianchi
F
F
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044482:Benzeneacetamides; D001593:Benzyl Compounds / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D044482:Benzeneacetamides; D001593:Benzyl Compounds; D011437:Propylamines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009020:Morphine; C067749:fedotozine; C045444:U 69593; D000109:Acetylcholine