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• W2004202269 abstract "The mechanism of action of the dimeric enkephalin peptide, biphalin (Tyr-D-Ala-Gly-Phe-NH2)2, which was previously shown to have remarkable high antinociceptive potency and low dependence liability in vivo, has now been studied by electrophysiologic analyses of its effects on the action potential duration (APD) of nociceptive types of sensory dorsal root ganglion (DRG) neurons in culture. Acute application of biphalin (pM-microM) elicited only dose-dependent, naloxone-reversible inhibitory (APD-shortening) effects on DRG neurons. Furthermore, at pM concentrations that evoked little or no alteration of the APD of DRG neurons biphalin selectively antagonized excitatory (APD-prolonging) effects of low (fM-nM) concentrations of bimodally-acting mu and delta opioid agonists and unmasked potent inhibitory effects of these opioids. This dual opioid inhibitory-agonist/excitatory-antagonist property of biphalin is remarkably similar to that previously observed in studies of the ultra-potent opioid analgesic, etorphine on DRG neurons and in sharp contrast to the excitatory agonist action of most mu, delta and kappa opioid alkaloids and peptides when tested at low (pM-nM) concentrations. Chronic treatment of DRG neurons with high (microM) concentrations of biphalin did not result in supersensitivity to the excitatory effects of naloxone nor in tolerance to opioid inhibition effects, in contrast to the excitatory opioid supersensitivity and tolerance that develop in chronic morphine- or DADLE-treated, but not chronic etorphine-treated, neurons. These studies on DRG neurons in vitro may help to account for the unexpectedly high antinociceptive potency and low dependence liability of biphalin as well as etorphine in vivo." @default.
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• W2004202269 date "1995-12-01" @default.
• W2004202269 modified "2023-10-08" @default.
• W2004202269 title "Biphalin, an enkephalin analog with unexpectedly high antinociceptive potency and low dependence liability in vivo, selectively antagonizes excitatory opioid receptor functions of sensory neurons in culture" @default.
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• W2004202269 doi "https://doi.org/10.1016/0006-8993(95)00999-1" @default.
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