A new tridecapeptide with an octaarginine vector has analgesic therapeutic potential and prevents morphine-induced tolerance
| Autor: | Vladimir A. Kashkin, Marina N. Makarova, Ivan I. Eliseev, Michail I. Titov, Yuri B. Porozov, Maxim Gureev, Elena V. Shekunova, Valery G. Makarov |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Physiology Analgesic Pharmacology Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Animals Medicine Rats Wistar Receptor Analgesics Drug Carriers business.industry Chronic pain Visceral pain medicine.disease Acute Pain Rats nervous system diseases Disease Models Animal 030104 developmental biology Nociception Neuropathic pain Morphine Neuralgia NMDA receptor Chronic Pain medicine.symptom Peptides business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Peptides. 99:61-69 |
| ISSN: | 0196-9781 |
| DOI: | 10.1016/j.peptides.2017.11.011 |
| Popis: | A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-d-Arg-Phe-Gly-NH2 was modified with the inclusion of a (d-Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (d-Arg)8 (tridecapeptide, TDP) in experimental models of acute and chronic pain. The analgesic effects of TDP were estimated using a model of acute visceral pain in mice (writhing test) and a model of chronic neuropathic pain (chronic constriction injury (CCI) of the sciatic nerve) in rats. The intravenous administration of morphine (0.32-1mg/kg) and TDP (0.32-1.8mg/kg) produced significant dose-related antinociceptive effects in the writhing test. The potency of TDP after i.g. administration was lower than that after i.v. administration but comparable with that of i.g. morphine. In the CCI model, TDP (0.1, 1 and 10mg/kg, i.g.) induced marked analgesia with repeated administration without any signs of tolerance. The single administration of TDP after morphine treatment (7days) produced a significant analgesic effect in morphine-tolerant rats, indicating the absence of cross-tolerance between these two drugs. The combined administration of TDP and morphine resulted in the reduction of analgesic tolerance to morphine. The absence of cross-tolerance to morphine and the ability to prevent morphine tolerance allows this compound to be a prospective candidate for chronic pain therapy. In order to find the target receptors for TDP, a docking study was performed. It was found that the molecule can bind to the NMDA receptor using electrostatic, hydrogen bonding and hydrophobic interactions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect