Antinociceptive effects of the kappa-opioid receptor agonist RP 60180 compared with pentazocine in an experimental human pain model.
Agonists at kappa-opioid receptors may preserve the analgesic properties of mu-opioidergic agonists while avoiding their major adverse effects. The present study was aimed to investigate the antinociceptive effects of the new kappa-opioid receptor agonist RP 60180. An experimental pain model was used based on specific pain stimuli and event-related potentials. Effects of RP 60180 were compared to placebo and to pentazocine that served as positive control. Twenty healthy male volunteers participated in a placebo-controlled, randomized, double-blind, five-way cross-over study. Single peroral doses of RP 60180 (0.1, 0.5, and 1.0 mg), pentazocine (50 mg), and placebo were administered. Pain was induced by means of short pulses of gaseous CO2 applied to the nasal mucosa. In response to these stimuli, chemo-somatosensory event-related potentials (CSSERP) and pain ratings were recorded. Maximum antinociceptive effects were observed 2 h after the administration of 1.0 mg of RP 60180 and 50 mg of pentazocine. This was shortly after RP 60180 had reached the maximum plasma concentration and when highest plasma concentrations of pentazocine were measured. Both RP 60180 and pentazocine reduced pain-related CSSERP amplitudes by approximately 40% at this time. Pentazocine tended to produce more side effects. These results indicate the potential therapeutic value of kappa-agonist analgesics.
Lötsch
J
J
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Ditterich
W
W
Hummel
T
T
Kobal
G
G
D000328:Adult; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D004311:Double-Blind Method; D005071:Evoked Potentials / Q000187:drug effects*; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D010423:Pentazocine / Q000009:adverse effects / Q000494:pharmacology*; D010640:Phenothiazines / Q000009:adverse effects / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists
D000700:Analgesics; D000701:Analgesics, Opioid; D006213:Hallucinogens; D010640:Phenothiazines; C098221:RP 60180; D017473:Receptors, Opioid, kappa; D010423:Pentazocine