A method to estimate the potency of the μ-component of an opioid having mixedμ-, andκ- and/orδ-agonist activities

Abstract

The SC administration of either typicalμ-agonists such as morphine, pethidine, fentanyl and levorphanol or a mixedμ- andδ-agonist like [d-Ala²,d-Leu⁵]-enkephalin to 10-day-old rats produced loss of righting reflex. Additionally, the loss of righting reflex induced by these opioid agonists was antagonized by naloxone, an opioid antagonist having a preference forμ-receptors, but by neither nor-binaltorphimine nor naltrindole, a specificκ- orδ-antagonist, respectively, indicating that the loss of righting reflex was produced by the interaction of an opioid withμ-receptors. Moreover, the potency of each opioid agonist relative to that of morphine estimated by the present in vivo method was similar to that determined by the traditional in vitro isolated preparation. In contrast toμ-agonists, neither typicalκ-agonists such as U-50, 488H, ketocyclazocine, pentazocine and butorphanol, nor a selectiveδ-agonist like [d-Pen²,d-Pen⁵]-enkephalin affected the righting reflex of 10-day-old rats, indicating thatμ-agonists, but neitherκ- norδ-agonists, produced the naloxone-reversible loss of righting reflex in infant rats. By employing the present in vivo method to estimate theμ-agonist activity of an opioid with mixed agonist activities, it was indicated that theμ-agonist activity of ethylketocyclazocine, which had been employed as a representativeκ-agonist, was essentially the same as that of morphine, a representativeμ-agonist.