SNC80: The Metabolic Role of a Nonpeptidic-ligand as a Highly Selective Delta-l Opioid Agonist
MetadataShow full item record
Hypoxic conditioning (HC), severe intermittent hypoxia, results in an increased hypoxic tolerance. Previous studies have shown HC to be dependent upon a central opioid pathway and have been strongly associated with a decrease in metabolic rate characterized by elevated plasma ketone levels, suggesting a possible alteration in respiratory quotient (RQ). The present study involved the pharmacological significance of a highly selective, nonpeptidic opioid delta-1 agonist, SNC80 ((( + )-4-[(9-alpha-R)-alpha-((2S,5RO-4-allyl-2,5-dimethyl-l-piperazinyl)-3- methoxybenzyl]-N,N-diethylbenzamide). Oxygen consumption (V02) and carbon dioxide production (VC02) were measured by a flow-through system to determine whether HC-like effects in mice could be induced with the administration of SNC80. Preliminary studies suggest HC dramatically reduces V02, VC02, and RQ for at least 24 minutes after conditioning. These experiments indicate that SNC80 significantly decreases both V02 and Ve02 by 4 minutes after injection and the parameters remain depressed from the 24 to the final 32 minute time point. These results partially support our hypothesis that SNC80 causes metabolic effects similar to those identified in hypoxically conditioned mice, in that reduced levels of V02 and VC02 are observed, yet the ambiguity of the RQ still remains to be explored. Although lowered RQ values are observed in SNC80-treated mice, speculations as to why the control groups experience a similar drop in RQ must be made.