Characterization of the effects of (+/-)-meptazinol, its individual enantiomers and N-methyl meptazinol on food consumption in the rat.

Both (+/-)-meptazinol (2 mg kg-1) and levorphanol (1 mg kg-1) produced hyperphagia over a 4 h period after intraperitoneal injection in free feeding rats during the daylight phase. The individual (+)- and (-)-enantiomers of meptazinol (2 mg kg-1 i.p.) induced comparable increases in cumulative food intake. N-methyl meptazinol (2-10 mg kg-1 i.p.), the quaternary analogue of meptazinol, produced no modification of food intake though it increased food consumption when injected intracerebroventricularly (10-100 micrograms per animal). Meptazinol and levorphanol hyperphagia was abolished by 1 mg kg-1 doses (i.p.) of the opioid antagonists naltrexone, naloxonazine and (-)-Mr 1452 but not by its (+)-enantiomer Mr 1453 which is not effective as an opioid antagonist. Intracerebroventricular administration of the delta-opioid antagonist ICI 154,129 (10 micrograms per animal) suppressed meptazinol but not levorphanol hyperphagia. It was concluded that meptazinol produces centrally mediated stereospecifically reversible hyperphagia through a mu-opioid receptor mechanism common to levorphanol, and also through delta-opioid receptor mechanism(s).