Role of 5-hydroxytryptamine receptors in narcotic-induced reduction in gastrointestinal transit in rats

Narcotic drugs are unique in inducing constipation. Morphine is known to induce a reduction in gastrointestinal transit through release of 5-hydroxytryptamine. A number of 5-HT antagonists, ketanserin, methysergide and MDL 72222 were used to investigate the role of 5-HT receptors in the morphine-induced reduction in intestinal propulsion. It was observed that ketanserin, at a dose of 5 mg/kg given subcutaneously, antagonized the effect of morphine on intestinal transit. Since ketanserin is a specific 5-HT2 receptor blocker, it appears that morphine produces this effect via activating the 5-HT2 receptors. The reduction in intestinal transit caused by the intrathecal administration of sufentanil appears to be mediated by 5-HT2 receptors because this effect is also antagonized by pretreatment with ketanserin. Thus this study indicates that 5-HT2 receptors in the intestine are responsible for the reduction in gastrointestinal transit.