Opioid Antagonist Properties of CTP, a Somatostatin Analog: In vivo Selectivity for Micron-Directed Ligands.

摘要

CTP (D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2), a conformationally constrained analog of somatostatin-14, has been shown to possess high affinity and selectivity for mu opioid receptors. Bioassay and in vivo studies have demonstrated that in addition to its weak somatostatin-like and delta agonist activities, CTP is a competitive mu opioid antagonist. The purpose of this study was to evaluate the mu antagonist properties of CTP in the rat maximal electroshock test (MES), an in vivo model which has been used to define mu, (DAGO), delta (DPDPE), and kappa (U50,488) receptor-selective anticonvulsant properties of opioids. Pretreatment with CTP, antagonized the anticonvulsant effects of the mu-selective opioid agonist DAGO in the rat MES test. The antagonist effects of CTP were potent and highly selective for the mu-directed ligand, having failed to attenuate the anticonvulsant effects of U50,488 (kappa) or DPDPE (delta). When given alone CTP was without effect on MES-induced convulsions. These results support the receptor binding, in vitro and in vivo profile of CTP as a selective mu opioid antagonist. Reprints. (AW)