Accession Number : ADA321554

Title :   Neural Responses to Injury: Prevention, Protection, and Repair. Volume 5: Neuropharmacology of Delta Receptor Agonists and Antagonists. Revised.

Descriptive Note : Annual technical rept. 20 Sep 94-19 Sep 95,

Corporate Author : LOUISIANA STATE UNIV MEDICAL CENTER NEW ORLEANS

Personal Author(s) : Bazan, Nicolas G. ; Moerschbaecher, Joseph

PDF Url : ADA321554

Report Date : JAN 1996

Pagination or Media Count : 62

Abstract : Studies in the Division of Neuropharmacology are investigating the role of endogenous opioid systems in learning and memory, ventilatory function and antinociception. The goal of these studies is: to identify and characterize candidate ligands that might be useful in studies on delta opioid mechanisms; and to use these compounds to systematically investigate the role of delta systems in complex behavioral processes, in respiration and in the perception of noxious stimuli. The first candidate compound was BW373U86, which is a highly-selective agonist for the delta opioid receptor. BW373U86 has effects that are unlike effects obtained with prototypic mu or kappa opioid agonists. This year, the candidate compound which was focused upon was OHM3507. This compound differs from morphine in terms of its effects on the immune system. It was hypothesized that this difference might be due to activity at the delta opioid receptor. The pharmacologic and behavioral effects of the fentanyl derivative OHM3507 were assessed to determine if this compound had increased antinociceptive effects and a reduced number of undesirable effects (e.g., respiratory depression) as compared to the prototypic opioids (e.g., fentanyl, morphine). The current studies were undertaken to determine the opioid receptor selectivity of OHM3507 using behavioral assays in rhesus monkey. At a dose of 0.32 mg/kg, OHM3507 produced 100% antinociception (20s latency) in monkeys and reduced minute volume respiration to <60% in both air and 5% CO2 in 02. In subjects treated daily with morphine (3.2 mg/kg) discriminating between saline and 0.01 mg/kg naltrexone, OHM3507 attenuated responding on the naltrexone-associated lever in a dose-dependent manner.

Descriptors :   *NERVOUS SYSTEM, *WOUNDS AND INJURIES, *STIMULI, *PHARMACOLOGY, MEMORY(PSYCHOLOGY), LIGANDS, DOSAGE, BEHAVIOR, NEUROLOGY, RESPIRATION, IMMUNITY, FOOD, LEARNING, PERCEPTION, ASSAYING, SENSE ORGANS, RHESUS MONKEYS, MONKEYS, CONDITIONING(LEARNING), MORPHINE.

Subject Categories : Medicine and Medical Research
      Stress Physiology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE