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• W1969663022 endingPage "1904" @default.
• W1969663022 startingPage "1898" @default.
• W1969663022 abstract "We previously described two novel analogues of endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, 1), modified with an 8-carbon lipoamino acid (C8LAA) with or without replacement of Tyr1 with 2,6-dimethyltyrosine (Dmt) at the N-terminus of the peptide (compounds 3 and 4, respectively). They were shown to be more stable and permeable, and acted as potent μ-opioid receptor agonists. In this study we report that the C8LAA modification resulted in successful systemic delivery of both analogues. They produced potent dose-dependent pain relief in a chronic constriction injury-rat model of neuropathic pain after intravenous administration with ED50 values obtained at 6.58 (±1.22) μmol/kg for 3 and 6.18 (±1.17) μmol/kg for 4. Using two different rat models of constipation that assess the effects of μ-opioid receptor agonists on stool hydration and gastro-intestinal motility, compound 3 produced insignificant constipation at 16 μmol/kg, whereas morphine elicited significant constipation at 2 μmol/kg. Compound 3 in contrast to morphine, did not attenuate the hypercapnic ventilatory response at 5 μmol/kg, a dose that fully alleviated hindpaw sensitivity at the time of peak effect in CCI-rats. This finding revealed the lack of respiratory depression effect at antinociceptive dose." @default.
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• W1969663022 date "2013-04-01" @default.
• W1969663022 modified "2023-09-26" @default.
• W1969663022 title "Peripherally acting novel lipo-endomorphin-1 peptides in neuropathic pain without producing constipation" @default.
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• W1969663022 doi "https://doi.org/10.1016/j.bmc.2013.01.044" @default.
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