Effects of the long-lasting kappa opioid 2-(3,4-dichlorophenyl)-N-methyl-N- [(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl) ethyl] acetamide in a drug discrimination and warm water tail-withdrawal procedure

Although studies suggest that 2-(3,4-dichlorophenyl-N-methyl-N-[(1S)-1-(3- isothiocyanatophenyl)-2-(1-pyrrolidinyl) ethyl] acetamide (DIPPA) has transient κ-opioid-mediated agonist effects followed by long-lasting κ-antagonist effects, its behavioral and pharmacological actions have not been systematically examined and there is evidence suggesting that some of its effects are species dependent The purpose of this investigation was to examine the actions of DIPPA in different behavioral procedures and in three species. In a pigeon drug discrimination procedure, DIPPA and the κ-opioids U50,488 and ICI-199441 substituted fully for the stimulus effects produced by spiradoline. For DIPPA, this effect was observed between 0.25 and 4 h after administration. In a warm water tail-withdrawal procedure, DIPPA failed to produce antinociception in rats or mice even when relatively high doses were tested using pretreatment intervals ranging from 0.25 to 24 h. In this procedure, DIPPA antagonized the effects of spiradoline and U50,488 in mice. In rats, DIPPA antagonized the effects of U50,488 but not those of spiradoline. Taken together, these results suggest that DIPPA may function as a low-efficacy κ-opioid and have a long duration of action, and there may be some species differences in its behavioral profile. This profile of action, however, differs from other low-efficacy κ-opioids.