Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys

Eduardo R. Butelman, S. Stevens Negus, John W. Lewis, James H. Woods

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The antagonist effects of clocinnamox were evaluated against opioid agonists, acting at μ, κ and δ-receptors, in rhesus monkeys (n=3-4) responding under a fixed-ratio 30 (FR 30) schedule for food delivery. Clocinnamox (0.032-0.1 mg/kg) dose-dependently antagonized fentanyl (0.001-0.32 mg/kg) after either a 3-h or 1-day pretreatment; there was substantial recovery of agonist potency by 1 week after clocinnamox. Etonitazene (0.0001-0.01 mg/kg) was also antagonized by clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The smaller extent of antagonism was not due to the appearance of non μ-opioid response-decreasing effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg) shifted the etonitazene dose-effect curve in the presence of clocinnamox (0.1 mg/kg). Clocinnamox (0.1-0.32 mg/kg) did not antagonize the rate-suppressing effects of the δ-agonist BW373U86 (0.0.01-1.0 mg/kg) or the κ-agonist U69,593 (0.001-0.032 mg/kg). These results are consistent with previous in vivo and in vitro evidence that characterized clocinnamox as an insurmountable antagonist, with selectivity for μ-over κ- and δ-receptors.

Original languageEnglish (US)
Pages (from-to)320-324
Number of pages5
Issue number4
StatePublished - 1996
Externally publishedYes


  • Clocinnamox
  • Fentanyl
  • Irreversible antagonists
  • Operant behavior
  • Rhesus monkeys

ASJC Scopus subject areas

  • Pharmacology


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