Substitution and primary dependence studies in animals

James H. Woods, Debra E. Gmerek

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


The mixed agonist-antagonist analgesics buprenorphine, butorphanol, nalbuphine, pentazocine and picenadol were compared to the prototype mu and kappa agonists morphine and Mr 2033, respectively, in the following tests in rhesus monkeys: overt behavioral effects upon acute administration in drug-naive animals; discriminative stimulus properties in monkeys trained to respond to either etorphine or ethylketazocine; self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug-naive animals. Whereas both buprenorphine and nalbuphine precipitate withdrawal in morphine-dependent monkeys, withdrawal following chronic administration of buprenorphine resulted in no observable signs of abstinence, while nalbuphine withdrawal was similar to that seen in morphine-dependent monkeys. Butorphanol, pentazocine and picenadol all produced mild dependence of the kappa-type; that is, natural withdrawal behavior similar to that seen following chronic Mr 2033 administration.

Original languageEnglish (US)
Pages (from-to)233-247
Number of pages15
JournalDrug and Alcohol Dependence
Issue number3-4
StatePublished - Feb 1985
Externally publishedYes


  • Buprenorphine
  • Butorphanol
  • Dependence
  • Mixed agonist-antagonist analgesic
  • Morphine
  • Mr 2033 (UM 1072)
  • Nalbuphine
  • Pentazocine
  • Picenadol
  • Rhesus monkey

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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