Clonidine and Dexmedetomidine Potently Inhibit Peristalsis in the Guinea Pig Ileum In Vitro

Background: Inhibition of intestinal peristalsis is a major side effect of drugs used for anesthesia or for analgesia and sedation of patients in the intensive care unit. This in vitro study examined the effect of clonidine and dexmedetomidine on intestinal peristalsis and analyzed some of their mechanisms of action.

Methods: In isolated segments of the guinea pig small intestine, peristalsis was triggered by a perfusion-induced rise of the intraluminal pressure. The peristaltic pressure threshold to elicit a peristaltic wave was used to quantify drug effects on peristalsis. Vehicle (Tyrode's solution), clonidine (10 nm-100 [mu]m), or dexmedetomidine (0.1-100 nm) were added extraserosally to the organ bath. In other series of experiments, clonidine or dexmedetomidine was administered after pretreatment with yohimbine, prazosin, apamin, naloxone, or vehicle. Clonidine was also tested after blockade of NO synthase with l-NAME and in the presence of the inactive enantiomer d-NAME.

Results: Clonidine and dexmedetomidine concentration-dependently increased peristaltic pressure threshold and inhibited peristalsis (clonidine: EC50 = 19.6 [mu]m; dexmedetomidine: EC50 = 12.0 nm). The inhibition caused by clonidine could be prevented by pretreatment with yohimbine, naloxone, and apamin, but not by prazosin, l-NAME, or d-NAME. Inhibition caused by dexmedetomidine was prevented by yohimbine only.