A new tridecapeptide with an octaarginine vector has analgesic therapeutic potential and prevents morphine-induced tolerance
Kashkin V. A., Shekunova E. V., Titov M. I., Eliseev I. I., Gureev M. A., Porozov Yu. B., Makarova M. N., Makarov V. G.
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1016/j.peptides.2017.11.011
Аннотация:
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 (0.32–1 mg/kg) and TDP (0.32–1.8 mg/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 wi
Ключевые слова:
CCI; Morphine tolerance; Opioids; Poly-arginine; Tridecapeptide
analgesic agent; arginine; kappa opiate receptor; morphine; mu opiate receptor; naloxone; peptide; proteinase; tetrapeptide; tridecapeptide; unclassified drug; analgesic agent; drug carrier; peptide; analgesic activity; animal experiment; animal model; antinociception; Article; chronic constriction injury; chronic pain; drug bioavailability; drug cross tolerance; drug potency; experimental neuropathic pain; high performance liquid chromatography; hydrogen bond; ion exchange chromatography; male; mouse; nonhuman; priority journal; visceral pain; writhing test; animal; chemistry; disease model; metabolism; neuralgia; pain; pathology; rat; Wistar rat; Acute Pain; Analgesics; Animals; Chronic Pain; Disease Models, Animal; Drug Carriers; Male; Neuralgia; Peptides; Rats; Rats, Wistar
Язык текста: Английский
ISSN: 1873-5169
Kashkin V. A.
Shekunova E. V.
Titov M. I.
Eliseev I. I.
Gureev M. A. Maksim Aleksandrovich 1989-
Porozov Yu. B. Yurij Borisovich 1970-
Makarova M. N.
Makarov V. G.
Кашкин В. А.
Шекунова Е. В.
Титов М. И.
Елисеев И. И.
Гуреев М. А. Максим Александрович 1989-
Порозов Ю. Б. Юрий Борисович 1970-
Макарова М. Н.
Макаров В. Г.
A new tridecapeptide with an octaarginine vector has analgesic therapeutic potential and prevents morphine-induced tolerance
Текст визуальный непосредственный
Peptides
Elsevier Science Publisher B.V.
Vol.99 P. 61-69
2018
Статья
CCI Morphine tolerance Opioids Poly-arginine Tridecapeptide
analgesic agent arginine kappa opiate receptor morphine mu opiate receptor naloxone peptide proteinase tetrapeptide tridecapeptide unclassified drug analgesic agent drug carrier peptide analgesic activity animal experiment animal model antinociception Article chronic constriction injury chronic pain drug bioavailability drug cross tolerance drug potency experimental neuropathic pain high performance liquid chromatography hydrogen bond ion exchange chromatography male mouse nonhuman priority journal visceral pain writhing test animal chemistry disease model metabolism neuralgia pain pathology rat Wistar rat Acute Pain Analgesics Animals Chronic Pain Disease Models, Animal Drug Carriers Male Neuralgia Peptides Rats Rats, Wistar
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 (0.32–1 mg/kg) and TDP (0.32–1.8 mg/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 wi