ALKALOID DELTA-AGONIST BW373U86 INCREASES HYPOXIC TOLERANCE

Activation of delta opioid receptors increases survival time during ac ute, lethal hypoxia in mice. delta Agonists therefore present a promis ing avenue for therapeutic application to reduce the morbidity and mor tality associated with clinical hypoxia in settings such as drowning h ead injury apnea, and complicated childbirths. However, most delta ago nists now available are peptides, and may have limited clinical utilit y. In the present study, we evaluate the neuroprotective ability of an alkaloid delta agonist, BW373U86. Alkaloid compounds, due to increase d stability and increased systemic distribution, may be more favorable for clinical use. We found that BW373U86, like the peptide delta agon ist, DPDPE ([D-Pen(2),D-Pen(5)]-enkephalin), increases survival time o f mice during lethal hypoxia. The mechanism of neuroprotection induced by delta receptor activation appears to involve decreasing body tempe rature. Further, using selective opioid receptor antagonists, it appea rs that BW373U86 exerts these neuroprotective effects by acting at del ta-opioid receptors.