Properties of a selective kappa agonist, U-50,488H

doi:10.1016/0024-3205(82)90132-1

Life Sciences

Volume 31, Issues 20–21, 15–22 November 1982, Pages 2257-2260

https://doi.org/10.1016/0024-3205(82)90132-1 Get rights and content

Abstract

U-50,488H has been shown to be a naloxone antagonizable analgesic in rodents. However, the dose of naloxone needed for antagonism is higher than it is for morphine. U-50,488H does not produce physical dependence; however it does produce tolerance upon chronic administration. U-50,488H is cross tolerant with bremazocine but not with morphine. Monkeys trained to discriminate ethylketocyclazocine (EKC) from saline show a complete generalization to U-50,488H but not to morphine. The evaluation of U-50,488H in ³H-EKC site-selective binding indicated that U-50,488H has a high affinity for the kappa receptor (Ki=114 nM) and a low affinity for the mu receptor (Ki=6100 nM). The ratio of Ku/Kk was 0.08 for morphine, 0.4 for dynorphin, and 53.5 for U-50,488H. The data suggest that U-50,488H is a selective agonist at the opioid kappa receptor.

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Properties of a selective kappa agonist, U-50,488H

Abstract

Eur. J. Pharmacol.

Life Sci.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

J. Pharmacol. exp. Ther.

J. Pharmacol. exp. Ther.

Arch. int. Pharmacodyn.