RELATIVE ANALGESIC POTENCY OF MU-OPIOIDS, DELTA-OPIOIDS AND KAPPA-OPIOIDS AFTER SPINAL ADMINISTRATION IN AMPHIBIANS

The analgesic effects of 12 opioid agonists in amphibians were measure d using the acetic acid test. Spinal administration of dermorphin, [D- Ala(2),NMePhe(4),Gly-ol]-enkephalin, fentanyl and morphine (mu opioids ); [D-Ser(2),Leu(5)-Thr(6)]-enkephalin, [D-Ala(2),D-Leu(5)]-enkephalin , [D-Pen(2),D-Pen(5)]-enkephalin and deltorphin (delta opioids); and C I977 {(5R)-(544 alpha,744 alpha,845 nyl)-1-oxaspiro[4,5]dec-8yl]-4-ben zofuranacetamide monohydrochloride, bremazocine}, U50488 -N-[2-(1-pyrr olidinyl)-cyclohexyl]benzeneacetamide methanesulfonate) and nalorphine (kappa opioids) produced a dose-dependent and long-lasting analgesia in the Northern grass frog, Rana pipiens. With all opioids, time cours e experiments showed that this analgesic effect lasted for at]east 4 h r, with no untoward effects observed within each dosage range used. Th e analgesic effects of the 12 opioids were blocked by systemic naltrex one pretreatment. Comparison of dose-response curves demonstrated that the rank order of potency was such that, in general, mu opioids > del ta opioids > kappa opioids. Dose-response curves obtained in the prese nce of a fixed dose of naltrexone showed the greatest shift for [D-Ser (2),Leu(5)-Thr(6)]-enkephalin, less so for [D-Ala(2),NMePhe(4),Gly-ol] -enkephalin and the least shift for bremazocine. ED(50) values for mu and delta opioids in the amphibian acetic acid test were significantly correlated to ED(50) values of the same opioids reported in the liter ature for the rodent TF test. These results show that a spinal site of opioid analgesia is present in amphibians and supports the utility of this alternative, nonmammalian model for studies of opioid analgesia and pain research.