Role of nitric oxide in gastrokinetic effects of the new benzoxepine derivative exepanol hydrochloride.
The gastrokinetic effects of exepanol hydrochloride (rac. 3,5-cis-2,3,4,5-tetrahydro-3-methyl-amino-1-benzoxepine-5-ol hydrochloride, CAS 77416-65-0, KC 2450) on gastrointestinal motility were studied both in vivo and in vitro. Exepanol-HCl accelerated the gastrointestinal (GI) transit in vivo in mice. This effect of exepanol-HCl was reduced by atropine, hemicholinium-3, morphine and MCN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyl trimethyl ammonium chloride). In guinea pig (GP) ileum, exepanol-HCl facilitated the peristaltic reflex to threshold pressures and restored the reflex in fatigued preparations. These effects of exepanol-HCl were compared with metoclopramide (MCP) which was used as reference compound in both in vivo and in vitro experiments. Exepanol-HCl also partially reversed the L-arginine induced tonic "hump' responses of GP ileum to transmural stimulation. These findings suggest a cholinergic involvement and a partial role of nitric oxide in the mechanism of action of exepantol-HCl on GI motility.
Chaudhuri
L
L
Pharmacology Division, Indian Institute of Chemical Biology, Calcutta, India.
Vedasiromoni
J R
JR
Besra
S E
SE
Ganguly
D K
DK
D000818:Animals; D001584:Benzoxepins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010528:Peristalsis / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D001584:Benzoxepins; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C045026:exepanol; D019001:Nitric Oxide Synthase