title: Naltrexone and beta-funaltrexamine antagonism of the antinociceptive and response rate-decreasing effects of morphine, dezocine, and d-propoxyphene.
abstract: BACKGROUND
  Patterns of competitive and insurmountable antagonism provide important data to guide the classification and characterization of different types of opioid agonists as well as infer the mechanism of action for agonists.
  
  
  OBJECTIVE
  Experiments with the competitive antagonist, naltrexone, and the insurmountable antagonist, beta-funaltrexamine (beta-FNA), were conducted to determine whether the antinociceptive and rate-decreasing effects of the opioid agonists dezocine and d-propoxyphene are 1) mediated through muu opioid receptors in rats, and 2) differ from morphine with respect to relative efficacy.
  
  
  METHODS
  The rat tail-withdrawal assay was used to measure antinociception and a fixed ratio 20 (FR20) schedule of food delivery was used to measure rate suppression.
  
  
  RESULTS
  Naltrexone (0.01-1.0 mg/kg) was approximately equipotent as an antagonist of the antinociceptive and rate-decreasing effects of both morphine and dezocine and as an antagonist of the antinociceptive effects of d-propoxyphene. Naltrexone failed to block the rate-decreasing effects of d-propoxyphene. beta-FNA (5 and 10 mg/kg) also antagonized the antinociceptive and rate-decreasing effects of morphine and dezocine as well as the antinociceptive effects of d-propoxyphene. beta-FNA failed to produce a dose-dependent antagonism of the rate-decreasing effects of d-propoxyphene.
  
  
  CONCLUSIONS
  These data suggest that the antinociceptive effects of morphine, dezocine, and d-propoxyphene and the rate-decreasing effects of morphine and dezocine are mediated through mu opioid receptors. Overall, high doses of beta-FNA produced a greater degree of antagonism of the behavioral effects of dezocine than morphine or d-propoxyphene, confirming other reports that dezocine is a lower efficacy agonist than morphine. Additionally, the degree of antagonism produced by beta-FNA was greater for the antinociceptive effects of all three compounds than for the rate-decreasing effects.
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill, 27599-3270, USA. ewalker@email.unc.edu
authors.forename: E A
authors.initials: EA
authors.lastname: Walker
authors.forename: M J
authors.initials: MJ
authors.lastname: Tiano
authors.forename: S I
authors.initials: SI
authors.lastname: Benyas
authors.forename: L A
authors.initials: LA
authors.lastname: Dykstra
authors.forename: M J
authors.initials: MJ
authors.lastname: Picker
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D051381:Rats
chemical_list: D009271:Naltrexone; C024524:beta-funaltrexamine