Different actions of 2 antidiarrheal agents, lidamidine and loperamide, on motility of the isolated cat colon muscle.

Besides their action on intestinal absorption and secretion antidiarrheal agents may affect gastrointestinal motility. Little is known about motor actions in the large intestine. Therefore, the effects of loperamide and lidamidine on contractile and myoelectrical activity were studied in strips of the circular muscle of the cat colon in vitro. Both drugs caused a concentration dependent increase in spontaneous contractions, but the potency of loperamide was greater than that of lidamidine and the efficacy of lidamidine greater than that of loperamide. The corresponding EC50 were 2.9 X 10(-9) M and 1.4 X 10(-5) M, respectively, and the EC100 2.7 X 10(-7) M and 10(-4) M, respectively. In the myoelectrical tracings loperamide stimulated predominantly spike activity, lidamidine oscillatory potentials. The effect of loperamide was antagonized by naloxone, thus indicating an action on opiate receptors. The effect of lidamidine was not inhibited by a variety of drugs. Tetrodotoxin and alpha-adrenergic inhibitors even exaggerated the lidamidine effect, probably by a suppression of tonic nervous inhibition. The receptor for the lidamidine action has yet to be determined. In conclusion, the motor effects may play an important role in the antidiarrheal action of loperamide, but probably not in that of lidamidine, at least not within the range of clinically used doses.