TY - JOUR
T1 - Ketazocines and morphine
T2 - Effects on gastrointestinal transit after central and peripheral administration
AU - Porreca, Frank
AU - Cowan, Alan
AU - Raffa, Robert B.
AU - Tallarida, Ronald J.
N1 - Funding Information:
Drs. J.C. Doxey and G. Metcalf were associated with the study at its inception. Generous samples of ketocyclazocine and EK were obtained from Sterling-Winthrop. Naloxone and phenazocine were gifts from Endo and Smith Kline & French, respectively. This work was supported by Grant DA 02322 from the National Institute on Drug Abuse.
PY - 1983/4/11
Y1 - 1983/4/11
N2 - 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.
AB - 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.
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U2 - 10.1016/0024-3205(83)90843-3
DO - 10.1016/0024-3205(83)90843-3
M3 - Article
C2 - 6339861
AN - SCOPUS:0020640892
SN - 0024-3205
VL - 32
SP - 1785
EP - 1790
JO - Life Sciences
JF - Life Sciences
IS - 15
ER -