Effect of dextromethorphan and levomethorphan on gastric emptying and intestinal transit in the rat

Dextromethorphan and levomethorphan were evaluated using 51Cr as a marker for their effects on gastric emptying and intestinal transit in the rat. Levomethorphan at 10 mg/kg i.p. and 10 and 50 mg/kg p.o. significantly (P less than or equal to .05) inhibited gastric emptying; dextromethorphan did not inhibit gastric emptying at p.o. doses up to 100 mg/kg or i.p. doses up to 10 mg/kg. Naloxone (1 mg/kg i.p.) significantly antagonized the effect of p.o. levomethorphan (50 mg/kg). Levomethorphan (10 and 50 mg/kg p.o. and 1 and 10 mg/kg i.p.) significantly inhibited intestinal transit. Dextromethorphan significantly inhibited intestinal transit after p.o. (10, 50, 100, 200 mg/kg) and i.p. (50 mg/kg) administration. As in the case of gastric emptying, naloxone inhibited the effect of levomethorphan but did not alter the effect of dextromethorphan. Naloxone itself (1 mg/kg i.p.) did not affect gastric emptying or intestinal transit. The results suggest that levomethorphan exerts inhibitory effects on intestinal transit and gastric emptying that are probably mediated partly through an opiate mechanism whereas the effects of dextromethorphan may be mediated through a nonopiate mechanism of action.