Meptazinol: unusual in vivo opioid receptor activity at supraspinal and spinal sites

Systemic (1-10 mg/kg, s.c.), intracerebroventricular (i.c.v. 20-80 micrograms) and spinal intrathecal (i.t., 5-20 micrograms) administration of meptazinol hydrochloride produced dose-related inhibition of reflex contractions of the urinary bladder, recorded isometrically in urethane-anesthetized rats. The effects of meptazinol were reversed by naloxone administered by the same route. Indeed, this was achieved with intracerebroventricular or intrathecal administration of naloxone (2 micrograms), which also selectively antagonized the mu-receptor ligand [D-Ala2, MePhe4, Gly(ol)5]enkephalin (DAGO). However ICI 174,864 (3 micrograms, i.c.v. or i.t.), a delta-opioid receptor antagonist, did not affect the actions of meptazinol given intracerebroventricularly or intrathecally though it consistently abolished the equieffective actions of a selective delta-receptor ligand (2-D-penicillamine, 5-L-penicillamine) enkephalin (DPLPE). Naloxonazine (5 micrograms, i.c.v. or i.t.), an irreversible mu 1-opioid receptor antagonist, produced prolonged antagonism of the effects of DPLPE and meptazinol. The effects of DPLPE partially or completely recovered by 24 hr, indicating that naloxonazine produced prolonged antagonism of delta-opioid receptors. The effects of maptazinol however only recovered after 72 hr, suggesting that antagonism by naloxonazine of this ligand was irreversible and was mediated through a unique opioid receptor interaction. Subthreshold doses of meptazinol (10 micrograms, i.c.v.; 3 micrograms, i.t.) consistently antagonized the effects of morphine given intracerebroventricularly or intrathecally but not the equieffective doses of DPLPE or DAGO. These observations suggest that meptazinol inhibited reflex contractions of the bladder by supraspinal and spinal mu-opioid receptor activation. Furthermore, its agonistic effect and its antagonistic actions were compatible with interactions at a subpopulation of opioid receptors, possibly mu 1-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)