Unveiling the antinociceptive mechanisms of Methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate: insights from nociceptive assays in mice

Jarrar, Q and Ayoub, R and Jarrar, Y and Jaffal, H and Goh, K W and Long, Chiau Ming * and Moshawih, S and Sirhan, A (2024) Unveiling the antinociceptive mechanisms of Methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate: insights from nociceptive assays in mice. European Review for Medical and Pharmacological Sciences, 28 (5). pp. 2068-2083. ISSN 2284-0729

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Official URL: 10.26355/eurrev_202403_35620


Objective: Methyl-2-(4-chloro- phenyl)-5-benzoxazoleacetate (MCBA), a synthetic benzoxazole derivative with established antipsoriatic efficacy, was investigated for potential antinociceptive effects. This study employs various nociceptive assays in mice to elucidate MCBA's antinociceptive mechanisms. Materials and methods: MCBA's antinociceptive potential was tested against various nociception models induced by formalin, glutamate, capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor agonist, and phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator. It was then assessed using the hot plate test and examined within the acetic acid-induced writhing test. During the acetic acid-induced writhing test, MCBA was pre-challenged against selective receptor antagonists such as naloxone, caffeine, atropine, yohimbine, ondansetron, and haloperidol. It was also pre-challenged with ATP-sensitive potassium channel inhibitor (glibenclamide) to further elucidate its antinociceptive mechanism. Results: The results showed that oral administration of MCBA led to a dose-dependent and significant inhibition (p < 0.05) of nociceptive effects across all evaluated models at doses of 60, 120, and 240 mg/kg. Moreover, the efficacy of MCBA's antinociceptive potential was significantly counteracted (p < 0.0001) by specific antagonists: (i) directed at adenosinergic, alpha-2 adrenergic, and cholinergic receptors using caffeine, yohimbine, and atropine, respectively; and (ii) targeting ATP-sensitive potassium channels, employing glibenclamide. Antagonists aimed at opioidergic and serotoninergic receptors (naloxone and ondansetron, respectively) had poor utility in inhibiting antinociceptive activity. Conversely, the dopaminergic receptor antagonist haloperidol potentiated locomotor abnormalities associated with MCBA treatment. Conclusions: MCBA-induced antinociception involves modulation of glutamatergic-, TRVP1 receptors- and PKC-signaling pathways. It impacts adenosinergic, alpha-2 adrenergic, and cholinergic receptors and opens ATP-sensitive potassium channels.

Item Type: Article
Uncontrolled Keywords: Benzoxazole; anti-nociception; Adenosinergic receptors; Cholinergic receptors; glutamatergic signaling pathway; health care; wellbeing; medicine;
Subjects: Q Science > QP Physiology
R Medicine > RA Public aspects of medicine
R Medicine > RM Therapeutics. Pharmacology
Divisions: Others > Non Sunway Academics
Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020]
Depositing User: Ms Yong Yee Chan
Related URLs:
Date Deposited: 13 May 2024 00:04
Last Modified: 15 May 2024 06:44
URI: http://eprints.sunway.edu.my/id/eprint/2583

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