Opioid and non-opioid actions of loperamide on cholinergic nerve function in human isolated colon.

Using a radiolabelling technique it was possible to measure changes of cholinergic nerve activity in human isolated taenia coli muscle. Loperamide (1.9-97.3 microM) depressed release of acetylcholine produced by electrical field stimulation to a greater degree than morphine (0.13-130 microM). The effect of loperamide was only partially sensitive to naloxone. Loperamide (7.8 microM) demonstrated calcium channel blocking-like properties as shown by its antagonism of CaCl2-induced contractions of depolarised muscle. Although an established calcium channel antagonist, verapamil, was also able to depress cholinergic nerve activity, the concentration was considerably greater than required for antagonism of CaCl2 contractions. The depression of acetylcholine release by loperamide may contribute to its anti-diarrhoeal properties.