Ketazocines and morphine: Effects on gastrointestinal transit after central and peripheral administration

Frank Porreca, Alan Cowan, Robert B. Raffa, Ronald J. Tallarida

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Abstract

The mu agonist, morphine, and the prototype kappa agonists, ketocyclazocine and ethylketocyclazocine (EK), were studied for their effects on gastrointestinal transit. Following s.c. administration, both morphine (0.3-3 mg/kg) and ketocyclazocine (0.3-10 mg/kg) antagonized transit of an opaque marker through the small intestines of mice. Morphine (0.1-1 μg) was also effective after intracerebroventricular (icv) administration in mice whereas ketocyclazocine (0.3-30 μg) was not. Similarly, while both morphine (0.3-5 mg/kg) and EK (0.6-10 mg/kg) slowed transit after s.c. injection to rats, only morphine (1-10 μg), but not EK (0.3-300 μg), was active following icv administration. Icv infusion of the mu benzomorphan, phenazocine (10-100 μg), slowed transit in a dose-related manner. These results indicate that there may be an anatomically distinct distribution of receptors for benzomorphan kappa agonists in both the mouse and rat, with these opiate receptors not being located near the lateral cerebral ventricles. The difference in efficacy between morphine and ketazocines in slowing gastrointestinal transit after icv administration to rodents suggests that (a) inactivity in this endpoint is a characteristic of benzomorphan kappa compounds and (b) the model may serve as a useful screen when establishing in vivo profiles of kappa agonists in mice and rats.

Original languageEnglish (US)
Pages (from-to)1785-1790
Number of pages6
JournalLife Sciences
Volume32
Issue number15
DOIs
StatePublished - Apr 11 1983
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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