Neural Responses to Injury: Prevention, Protection and Repair; Volume 5: Neuropharmacology of Delta Receptor Agonists and Antagonists.
Annual rept. 20 Sep 95-19 Sep 96,
LOUISIANA STATE UNIV NEW ORLEANS
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The Division of Neuropharmacology is conducting studies on the role of endogenous opioid systems in learning and memory, ventilatory function and antinociception. The major goal of these studies is to identify and characterize novel ligands of delta opioid receptors for the explicit purpose of systematically investigating the role of delta opioid systems in complex behavioral processes, respiration and the perception of noxious stimuli. The first candidate compound was BW373U86, which is a highly-selective agonist for the delta opioid receptor. Although BW373U86 had effects that were unique from the effects obtained with prototypic mu or kappa opioid agonists, the behavioral and pharmacological profile for this agonist was disappointing. Therefore, this year, we examined the highly selective nonpeptidic ligand, SNC-80. This compound is the methyl ether of one enantiomer of BW3 73U86, but differs from BW3 73U86 in that it is systemically active and has demonstrated selectivity for the delta receptor that is comparable to that seen with delta-selective opioid peptides. Ventilation and antinociceptive studies with SNC-80 were conducted to determine if this full agonist at delta receptors was capable of increasing antinociceptive effects while at the same time reducing the number of undesirable effects e.g., respiratory depression as compared to prototypic opioids such as fentanyl and morphine. In the ventilation studies, 0.1-1 mglkg of SNC- 80 decreased all three measures of respiration in air in a dose-related manner.
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