Analeptic effect of opiate receptor agonists in rabbits

Eight opiate agonists, administered by the intracerebroventricular (i.c.v.) route, were evaluated as analeptics in pentobarbital-anesthetized rabbits. Morphine, codeine, ethylketocyclazocine, N-allylnormetazocine, meperidine and methadone, but not etorphine or D-Ala2-Met-enkephalin, given i.c.v. 40 min after pentobarbital (30 mg/kg i.v.), produced significant shortening of the duration of anesthesia as determined by the loss of the righting reflex. No apparent relationship was found between this and analgesic potency, nor with the specific receptor subtypes with which these agonists are known to interact. With active compounds, such as morphine, codeine and methadone, producing narcotic sedation, it was necessary to pretreat the animals with naltrexone to unmask the analeptic effect. It is concluded that the analeptic effect produced by certain opiate drugs is not specifically related to any of the subtypes of opiate receptors thus far described.