Antinociceptive models displaying peripheral opioid activity.

A writhing syndrome was induced in mice by intraperitoneal administration of carbacyclin (1-100 micrograms/kg), a potent stable analogue of prostacyclin. A quaternary opiate agonist and antagonist, N-methyl morphine and N-methyl nalorphine respectively, exhibited potent antinociceptive properties on subcutaneous administration in this model. Naloxone and naltrexone also displayed weak antinociceptive activity in carbacyclin-induced writhing. Given subcutaneously, N-methyl morphine, but not N-methyl nalorphine or naloxone, inhibited carrageenan-induced hyperalgesia in the rat paw. Thus, demonstration of the peripheral antinociceptive effects of quaternary morphine or nalorphine depends upon the experimental model used, in which small variations may affect the ability to exhibit such effects.