Effects of loperamide on the guinea pig taenia coli

The effects of an antidiarrhoeal agent, loperamide, were studied using isolated guinea pig taenia coli. Loperamide in concentrations ranging from 10(-7) M inhibited the cholinergic, contractile responses induced by electrical transmural stimulation, nicotine and serotonin, and the nonadrenergic, relaxing responses induced by electrical transmural stimulation and nicotine. However, the adrenergic response to perivascular nerve stimulation was not affected by these concentrations. The inhibitory effects of loperamide were not reversed by washing with a drug-free solution. Morphine (10(-6 M to 10(-5) M) also inhibited both cholinergic and nonadrenergic responses, but the effect was reversible. Naloxone (1o(-6) M) attenuated the inhibitory effects of both drugs. Unlike morphine, loperamide in concentrations higher than 5 x 10(-6) M relaxed the strips and reduced the contractile response to acetylcholine noncompetitively, and these effects were not blocked by naloxone. These results suggest that loperamide at low concentrations acts selectively on the opiate receptors located in both cholinergic and nonadrenergic nerves and at higher concentrations also acts directly on smooth muscle thus producing relaxation of the intestinal tone.