ROLE OF NITRIC-OXIDE IN GASTROKINETIC EFFECTS OF THE NEW BENZOXEPINE DERIVATIVE EXEPANOL HYDROCHLORIDE

The gastrokinetic effects of exepanol hydrochloride (rac. 3,4,5-tetrah ydro-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, hem icholinium-3, morphine and MCN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2 -butynyl trimethyl ammonium chloride). In guinea pig (GP) ileum, exepa nol-HCl facilitated the peristaltic reflex to threshold pressures and restored the reflex in fatigued preparations. These effects of exepano l-HCl were compared with metoclopramide (MCP) which was used as refere nce compound in both in vivo and in vitro experiments. Exepanol-HCl al so partially reversed the L-arginine induced tonic 'hump' responses of GP ileum to transmural stimulation. These findings suggest a choliner gic involvement and a partial role of nitric oxide in the mechanism of action of exepantol-HCl on GI motility.