Doherty N S, Hancock A A
J Pharmacol Exp Ther. 1983 May;225(2):269-74.
Oral administration of clonidine blocked diarrhea induced in mice by castor oil, prostaglandin E2, 5-hydroxytryptophan and bethanechol. The antidiarrheal action of clonidine was blocked by yohimbine but not by naloxone, propranolol, prazosin or cimetidine, indicating involvement of the alpha-2 adrenergic agonist activity of clonidine. Other alpha-2 adrenergic agonists (naphazoline, guanabenz, ergometrine, alpha-methylnorepinephrine) were also effective antidiarrheal agents, but alpha-1 (methoxamine, phenylephrine) or beta (isoproterenol) adrenergic agonists were not. Clonidine also blocked normal defecation in mice, an effect which was antagonized by yohimbine. Intracerebroventricular injection of clonidine produced no antidiarrheal effect, suggesting a peripheral site of action. Clonidine inhibited the distension-induced peristaltic reflex in the isolated guinea-pig ileum, an effect which was antagonized by yohimbine. The profound inhibition of peristaltic flow rate was due largely to inhibition of the rate of peristalsis, although an inhibition of the force of peristaltic contractions also contributed. This suggests that the inhibitory effects of alpha-2 adrenergic agonists on intestinal motility are due to the presence of inhibitory alpha-2 adrenergic receptors located on the pacemaker neurons of the enteric nervous system as well as presynaptically on postganglionic neurons innervating intestinal smooth muscle cells.
口服可乐定可阻断蓖麻油、前列腺素E2、5-羟色氨酸和氨甲酰甲胆碱诱导的小鼠腹泻。可乐定的止泻作用可被育亨宾阻断，但不能被纳洛酮、普萘洛尔、哌唑嗪或西咪替丁阻断，这表明可乐定的α-2肾上腺素能激动剂活性参与其中。其他α-2肾上腺素能激动剂（萘甲唑啉、胍那苄、麦角新碱、α-甲基去甲肾上腺素）也是有效的止泻剂，但α-1（甲氧明、去氧肾上腺素）或β（异丙肾上腺素）肾上腺素能激动剂则不是。可乐定还可阻断小鼠的正常排便，这一作用可被育亨宾拮抗。脑室内注射可乐定未产生止泻作用，提示其作用部位在周围。可乐定可抑制离体豚鼠回肠的扩张诱导蠕动反射，这一作用可被育亨宾拮抗。蠕动流速的显著抑制主要是由于蠕动速率的抑制，尽管蠕动收缩力的抑制也有一定作用。这表明α-2肾上腺素能激动剂对肠道运动的抑制作用是由于存在于肠神经系统起搏神经元以及支配肠道平滑肌细胞的节后神经元突触前的抑制性α-2肾上腺素能受体。
