Three structurally different peptide agonists of opioid receptors, i.e., gludalan, deltolei, and dalargin, were synthesized and assessed for infarction-limiting effects in rats with coronary occlusion (45 min) and reperfusion (2 h). The opioid peptides dalargin and gludalan (0.1 mg/kg) and deltolei (0.03, 0.1, and 0.2 mg/kg) were injected 5 min before reperfusion. It was found that gludalan and deltolei at a dose of 0.1 mg/kg decreased the ratio of infarction size to the area at risk (IS/AAR) whereas dalargin did not affect the IS. The infarction-limiting effect of deltolei disappeared if the peptide dose was decreased (0.03 mg/kg) or increased (0.2 mg/kg). The opioid receptor antagonists naltrexone (5 mg/kg) or naloxone methiodide (5 mg/kg), which does not penetrate the blood—brain barrier, eliminated the infarction-limiting effect of gludalan.
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Acknowledgments
The work was sponsored by the Russian Science Foundation No. 14-15-00008. Studies with dalargin were performed under State Task AAAA-A15-115120910024-0.
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 52, No. 4, pp. 3 – 6, April, 2018.
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Tsibul’nikov, S.Y., Mukhomedzyanov, A.V., Maslov, L.N. et al. Synthesis and Infarction-Limiting Properties of Peptide Agonists of Opioid Receptors. Pharm Chem J 52, 291–293 (2018). https://doi.org/10.1007/s11094-018-1808-3
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DOI: https://doi.org/10.1007/s11094-018-1808-3