Protective effect of telmisartan against morphine-induced analgesic tolerance in mice

Elif Nur Barut; Seçkin Engin; Yeşim Kaya Yaşar; Elif Gun; Mine Duman

Protective effect of telmisartan against morphine-induced analgesic tolerance in mice

Abstract

Morphine tolerance is a serious clinical problem characterized by a decreased analgesic effect resulted from the long-term use of morphine with uncertain etiology and therapeutic interventions are limited. In this study, we aimed to investigate the effect of telmisartan in a mouse model of morphine-induced analgesic tolerance and the underlying mechanisms of its action. Morphine (10 mg/kg) was injected subcutaneously twice daily for five days. Mice were pretreated with Telmisartan (TEL; 5 and 15 mg/kg) orally by gavage 30 min before each morphine injection. L-NAME (10 mg/kg), L-arginine (L-ARG,300 mg/kg) or N-acetylcysteine (NAC, 50 mg/kg) was administered intraperitoneally 45 min prior to morphine. Analgesic efficacy was evaluated by hot-plate test on 1st, 3rd and 5th days, 60 min after morphine injection. Spinal cord samples of mice were used to examine the protein expressions of nNOS and iNOS by western blotting and total GSH content. Repeated morphine administration caused a significant decrease in analgesic efficacy, demonstrating the development of morphine tolerance. High-dose TEL treatment effectively prevented morphine-induced analgesic tolerance. L-ARG abolished the inhibitory effect of TEL on morphine tolerance, while L- NAME and NAC did not alter. GSH level and nNOS expression were decreased, as well as iNOS expression was increased in the spinal cords from morphine-tolerant mice. TEL (15 mg/kg) treatment prevented the decrease in GSH level and the increase in iNOS expression of spinal cords. TEL would be a potential therapeutic candidate in preventing morphine tolerance through its activity on antioxidant systems and, in part, on the nitric oxide pathway.

Keywords

References

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Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Research Article

Authors

Elif Nur Barut ^*
0000-0003-3284-848X
Türkiye

Seçkin Engin
0000-0002-1982-7820
Türkiye

Yeşim Kaya Yaşar
0000-0002-9938-3288
Türkiye

Elif Gun This is me
0000-0003-4854-3701
Türkiye

Mine Duman
0000-0002-9057-0634
Türkiye

Publication Date

June 28, 2025

Submission Date

October 3, 2023

Acceptance Date

December 4, 2023

Published in Issue

Year 2024 Volume: 28 Number: 4

IZ

https://izlik.org/JA23EM66KF

Cite

RIS / Bibtex

APA

Barut, E. N., Engin, S., Kaya Yaşar, Y., Gun, E., & Duman, M. (2025). Protective effect of telmisartan against morphine-induced analgesic tolerance in mice. Journal of Research in Pharmacy, 28(4), 1079-1087. https://izlik.org/JA23EM66KF

AMA

1.Barut EN, Engin S, Kaya Yaşar Y, Gun E, Duman M. Protective effect of telmisartan against morphine-induced analgesic tolerance in mice. J. Res. Pharm. 2025;28(4):1079-1087. https://izlik.org/JA23EM66KF

Chicago

Barut, Elif Nur, Seçkin Engin, Yeşim Kaya Yaşar, Elif Gun, and Mine Duman. 2025. “Protective Effect of Telmisartan Against Morphine-Induced Analgesic Tolerance in Mice”. Journal of Research in Pharmacy 28 (4): 1079-87. https://izlik.org/JA23EM66KF.

EndNote

Barut EN, Engin S, Kaya Yaşar Y, Gun E, Duman M (July 1, 2025) Protective effect of telmisartan against morphine-induced analgesic tolerance in mice. Journal of Research in Pharmacy 28 4 1079–1087.

IEEE

[1]E. N. Barut, S. Engin, Y. Kaya Yaşar, E. Gun, and M. Duman, “Protective effect of telmisartan against morphine-induced analgesic tolerance in mice”, J. Res. Pharm., vol. 28, no. 4, pp. 1079–1087, July 2025, [Online]. Available: https://izlik.org/JA23EM66KF

ISNAD

Barut, Elif Nur - Engin, Seçkin - Kaya Yaşar, Yeşim - Gun, Elif - Duman, Mine. “Protective Effect of Telmisartan Against Morphine-Induced Analgesic Tolerance in Mice”. Journal of Research in Pharmacy 28/4 (July 1, 2025): 1079-1087. https://izlik.org/JA23EM66KF.

JAMA

1.Barut EN, Engin S, Kaya Yaşar Y, Gun E, Duman M. Protective effect of telmisartan against morphine-induced analgesic tolerance in mice. J. Res. Pharm. 2025;28:1079–1087.

MLA

Barut, Elif Nur, et al. “Protective Effect of Telmisartan Against Morphine-Induced Analgesic Tolerance in Mice”. Journal of Research in Pharmacy, vol. 28, no. 4, July 2025, pp. 1079-87, https://izlik.org/JA23EM66KF.

Vancouver

1.Elif Nur Barut, Seçkin Engin, Yeşim Kaya Yaşar, Elif Gun, Mine Duman. Protective effect of telmisartan against morphine-induced analgesic tolerance in mice. J. Res. Pharm. [Internet]. 2025 Jul. 1;28(4):1079-87. Available from: https://izlik.org/JA23EM66KF