title: Antinociceptive effects of the selective delta opioid agonist SNC80 alone and in combination with mu opioids in the squirrel monkey titration procedure.
abstract: BACKGROUND
  The nonpeptidic compound SNC80 [(+)-4[(alphaR)-alpha-((2S, 5R)-4-allyl-2, 5,-dimethyl-l-piperazinyl)-3-methoxybenzyl]- N, N-diethylbenzamide], has a high degree of selectivity for delta opioid receptors. Moreover, compounds with delta opioid activity have been shown to enhance the effects of mu agonists under certain conditions.
  
  
  OBJECTIVE
  The present study examined the effects of SNC80 alone and in combination with the mu opioid agonists, morphine, butorphanol, and buprenorphine to determine whether SNC80 would enhance their antinociceptive effects.
  
  
  METHODS
  In the squirrel monkey shock titration procedure increasing levels of shock are delivered to the monkey's tail in incremental steps and responses on a lever decrease shock intensity. The level at which monkeys maintain the shock (median shock level, MSL) and rate of responding (RR) are examined.
  
  
  RESULTS
  SNC80 alone did not consistently alter responding under the titration procedure; however, morphine, butorphanol, and buprenorphine increased MSL without decreasing RR markedly. SNC80 (0.1-3.0 mg/kg) enhanced the effects of single doses of morphine, butorphanol, and buprenorphine that either did not increase or produced very small increases in MSL when administered alone. Interestingly, SNC80 enhanced the effects of morphine, butorphanol, and buprenorphine on MSL without decreasing RR.
  
  
  CONCLUSIONS
  SNC80 does not produce antinociceptive effects in the squirrel monkey titration procedure but can enhance the effects of selected doses of morphine, butorphanol, and buprenorphine on MSL without decreasing RR. These data suggest that SNC80-induced enhancement of the antinociceptive effects of mu opioids is dependent on dose, time, and method of administration and is not the result of sedation or motor dysfunction.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, NC 27599-3270, USA. ldykstra@unc.edu
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dykstra
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Granger
authors.forename: Richard M
authors.initials: RM
authors.lastname: Allen
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D002047:Buprenorphine / Q000494:pharmacology; D002077:Butorphanol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012453:Saimiri; D013997:Time Factors
chemical_list: D000700:Analgesics; D001549:Benzamides; D009294:Narcotics; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D002047:Buprenorphine; D009020:Morphine; D002077:Butorphanol