naltrindole and linsidomine

Previous reports have indicated that the use of delta agonists may prove to be a viable therapeutic tool as an analgesic agent without conventional opioid side effects. In addition, recent evidence suggests that delta ligands may exert neuroprotective effects under a variety of toxin insults. The aim of the present studies was to assess the ability of delta agonists (peptide: [D-Pen(2,5)] enkephalin (DPDPE), non-peptide: (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80)) and antagonists (naltrindole) to modify dichlorofluorescein (DCFH) fluorescence in the presence of the peroxynitrite generator, 3-morpholinylsydnoneimine chloride (SIN-1) or HIV-protein, TAT(1-72) (TAT) in SK-N-SH cells. Both DPDPE (100 nM) and SNC-80 (250 nM) attenuated (30-50%) the increased oxidative stress in the presence of SIN-1. This effect was partially reversed by addition of naltrindole, suggesting involvement of delta receptors. Peroxynitrite radicals are involved in neurotoxicity associated with TAT. Incubation with TAT (10-250 nM) demonstrated a concentration-dependent increase in oxidative stress up to 200% over control values. Preincubation with delta agonists reduced 50 nM TAT-mediated oxidative stress 15-40%, which was partially reversed by naltrindole. Increasing log-concentrations of DPDPE or SNC-80 (0.01-100 microM) attenuated TAT-mediated oxidative stress up to 50% at 100 microM. In conclusion, these data demonstrate that both peptide and non-peptide delta agonists can partially attenuate intracellular oxidative stress, in part through a receptor-mediated mechanism. This suggests that delta ligands may have therapeutic usefulness in HIV patients beyond analgesia.

Topics: Benzamides; Cell Line, Tumor; Cell Membrane; Dose-Response Relationship, Drug; Enkephalin, D-Penicillamine (2,5)-; Fluoresceins; Free Radicals; Gene Products, tat; Humans; Molsidomine; Naltrexone; Narcotic Antagonists; Opioid Peptides; Oxidative Stress; Piperazines; Receptors, Opioid, delta; tat Gene Products, Human Immunodeficiency Virus