DIFFERENTIAL NEUROTOXICITY OF ETORPHINE-LIKE OPIATES - LACK OF CORRELATION WITH THEIR ABILITY TO ACTIVATE OPIATE RECEPTORS

The present study was undertaken to compare the neurotoxic effects of three etorphine-like opiates (etorphine, dihydroetorphine, and another derivative of oripavine) and heroin with their ability to activate op iate receptors in human neuroblastoma cell line SK-N-SH as well as in two other neuronal cell lines. Neurotoxicity was measured by using [H- 3]-thymidine incorporation analysis, cell viability measurement and Cy tosensor microphysiometry. It was found that, in spite of the very sim ilar molecular structures of these opiates, they displayed significant differences in cytotoxicity, with etorphine and another derivative of oripavine possessing high potency but dihydroetorphine and heroin lit tle effect. However, neurotoxic potency of the opiates was not directl y correlated to their ability to activate opioid receptors, as determi ned by [S-35]-guanylyl-5'-O-(gamma-tho)-triphosphate binding assay. Th ese findings provide clear evidence of differential neurotoxicity of e torphine-like opiates, and suggest that the neurotoxicity is not close ly related to the molecular configuration required as opioid receptor agonist but is probably associated with the presence of a double bond in the structure. (C) 1998 Elsevier Science Ltd. All rights reserved.