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Alkaloid delta agonist BW373U86 increases hypoxic tolerance
D M Bofetiado1, K P Mayfield, L G D'Alecy
1Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
Anesthesia and Analgesia
|June 1, 1996
Summary
Novel alkaloid delta agonists, like BW373U86, enhance survival during lethal hypoxia by activating delta opioid receptors. This neuroprotective effect, potentially useful in clinical settings, involves a decrease in body temperature.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Delta opioid receptor agonists increase survival during acute lethal hypoxia.
- Clinical applications for hypoxia are limited by peptide-based delta agonists.
- Alkaloid compounds offer potential advantages in stability and systemic distribution for therapeutic use.
Purpose of the Study:
- To evaluate the neuroprotective potential of the alkaloid delta agonist BW373U86.
- To compare the efficacy of BW373U86 with a peptide delta agonist (DPDPE).
- To elucidate the mechanism underlying BW373U86-induced neuroprotection.
Main Methods:
- Administered BW373U86 and DPDPE to mice exposed to lethal hypoxia.
- Monitored survival times and body temperature.
- Utilized selective opioid receptor antagonists to determine receptor specificity.
Main Results:
- BW373U86 significantly increased mouse survival time during lethal hypoxia, similar to DPDPE.
- Neuroprotection mediated by delta opioid receptor activation was associated with decreased body temperature.
- BW373U86's effects were confirmed to be mediated via delta-opioid receptors.
Conclusions:
- Alkaloid BW373U86 demonstrates neuroprotective effects against lethal hypoxia.
- BW373U86 represents a promising therapeutic candidate for clinical hypoxia due to its alkaloid nature.
- Delta opioid receptor activation, leading to hypothermia, is a key mechanism for hypoxia survival.