BENZODIAZEPINE-INDUCED INTESTINAL MOTOR DISTURBANCES IN RATS - MEDIATION BY OMEGA(2) (BZ(2)) SITES ON CAPSAICIN-SENSITIVE AFFERENT NEURONS

1 The central and peripheral effects of the omega (benzodiazepine) sit e ligands, clonazepam, alpidem, zolpidem, triazolam, flumazenil, ethyl beta carboline-3-carboxylate (beta-CCE) and N-methyl beta carboline-3 -carboxylate (beta-CCM) on intestinal myoelectrical activity were eval uated in conscious rats, chronically fitted with Nichrome electrodes i mplanted on the duodenum and jejunum. The localization of the omega (b enzodiazepine) receptors involved in these effects was evaluated by us e of systemic and perivagal capsaicin treatments. 2 When administered intraperitoneally (i.p.) the omega site inverse agonists beta-CCE and beta-CCM, and the omega site antagonist flumazenil, did not affect the duodeno-jejunal motility. Alpidem and zolpidem, two selective omega(1 ) site agonists induced an inhibition of migrating myoelectric complex es (MMCs) only at a high dose (5 mg kg(-1)). In contrast, clonazepam ( a mixed omega(1)/omega(2) agonist) and triazolam (a preferential omega (2) site agonist) disrupted the MMC-pattern at doses as low as 0.05 mg kg(-1), the effect of triazolam being of much longer duration than th at of clonazepam. None of these drugs altered MMC-pattern when adminis tered centrally (i.c.v.). 3 Administered i.p. or i.c.v. prior to triaz olam, alpidem blocked the effect of triazolam on duodenojejunal spike activity. Administered i.p. prior to triazolam, flumazenil suppressed the triazolam-induced MMC-disruption. Previous systemic but not periva gal capsaicin treatment suppressed the effects of clonazepam on MMCs. 4 It is concluded that omega-site agonists but not antagonist or inver se agonists, administered systemically induce intestinal motor disturb ances which may be linked to activation of omega(2) (BZ(2)) sites loca ted on nonvagal capsaicin-sensitive afferent neurones.