Pharmacological profile of PD 117302, a selective kappa-opioid agonist

1 PD 117302, a new nonpeptide opioid compound shown in in vitro studies to be a selective kappa-opioid agonist, has been evaluated in vivo for antinociceptive activity and other effects characteristic of kappa-receptor activation. 2 Dose-related long lasting antinociception was produced by PD 117302 against a mechanical noxious stimulus in rats following intravenous, subcutaneous or oral administration. 3 PD 117302 was effective in raising the nociceptive threshold to mechanical and chemical but not to thermal noxious stimuli in the mouse. This effect was attenuated in animals pretreated with the opioid antagonist naloxone. 4 In addition to producing antinociception, PD 117302 also caused naloxone-reversible locomotor impairment and diuresis, effects that are typical of kappa-agonists. 5 PD 117302 did not cause respiratory depression, inhibition of gastrointestinal motility or naloxone-precipatated withdrawal jumping in mice, effects that are associated with actions at the mu-opioid receptor. 6 The pharmacological profile of PD 117302 in vivo is consistent with in vitro data suggesting that PD 117302 is a selective agonist at the kappa-opioid receptor.