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.
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