Characterization of the effects of (±)‐meptazinol, its individual enantiomers and N‐methyl meptazinol on food consumption in the rat

Abstract

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 μg 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 δ‐opioid receptor antagonist ICI 154,129 (10 μg per animal) suppressed meptazinol but not levorphanol hyperphagia. It was concluded that meptazinol produces centrally mediated stereospecifically reversible hyperphagia through a μ‐opioid receptor mechanism common to levorphanol, and also through δ‐opioid receptor mechanism(s).