The actions of ketotifen on intestinal smooth muscles.
Ketotifen is a tricyclic drug with a wide spectrum of pharmacological effects. We studied the actions of ketotifen on the mechanical activity of isolated segments of guinea-pig ileum, guinea-pig colon and mouse colon. In the guinea-pig ileum ketotifen induced small contractions and inhibited the contractions induced by carbachol and by electric field stimulation. Responses to bradykinin (in the absence or in the presence of atropine 1 microM) were similarly inhibited by ketotifen, with an IC50 of 23 microM. In the guinea-pig colon ketotifen evoked non-cholinergic contractions with a pD2 of 4.5, but still it inhibited responses to bradykinin (IC50 = 75 microM). Ketotifen relaxed the unstimulated mouse colon with a pD2 of 4.2. This effect persisted in the presence of propranolol and phentolamine (each 10 microM). Incubation of the mouse colon with the nitric oxide synthase inhibitors NG-nitro-L-Arginine methyl ester hydrochloride (L-NAME), or L-NG-nitro-arginine (L-NNA) (100-500 microM) did not alter the inhibitory action of ketotifen. The histamine H1 receptor antagonist chlorpheniramine (5 microM) or the nerve blocker tetrodotoxin (1 microM) did not alter the inhibitory effects of ketotifen. It is concluded that the actions of ketotifen are mediated by a non-cholinergic, non-histaminergic mechanisms.
Abu-Dalu
R
R
Laboratory of Experimental Surgery, Hadassah University Hospital, Jerusalem, Israel.
Zhang
J M
JM
Hanani
M
M
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity
D007665:Ketotifen