Dataset Information

P2Y₁₄ Receptor Antagonists Reverse Chronic Neuropathic Pain in a Mouse Model.

ABSTRACT: Eight P2Y₁₄R antagonists, including three newly synthesized analogues, containing a naphthalene or phenyl-triazolyl scaffold were compared in a mouse model of chronic neuropathic pain (sciatic constriction). P2Y₁₄R antagonists rapidly (≤30 min) reversed mechano-allodynia, with maximal effects typically within 1 h after injection. Two analogues (4-[4-(4-piperidinyl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthalenecarboxylic acid 1 and N-acetyl analogue 4, 10 μmol/kg, i.p.) achieved complete pain reversal (100%) at 1 to 2 h, with relief evident up to 5 h for 4 (41%). A reversed triazole analogue 7 reached 87% maximal protection. Receptor affinity was determined using a fluorescent antagonist binding assay, indicating similar mouse and human P2Y₁₄R affinity. The mP2Y₁₄R affinity was only partially predictive of in vivo efficacy, suggesting the influence of pharmacokinetic factors. Thus P2Y₁₄R is a potential therapeutic target for treating chronic pain.

SUBMITTER: Mufti F

PROVIDER: S-EPMC7294700 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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P2Y14 Receptor Antagonists Reverse Chronic Neuropathic Pain in a Mouse Model.

Mufti Fatma F Jung Young-Hwan YH Giancotti Luigino Antonio LA Yu Jinha J Chen Zhoumou Z Phung Ngan B NB Jacobson Kenneth A KA Salvemini Daniela D

ACS medicinal chemistry letters 20200430 6

Eight P2Y14R antagonists, including three newly synthesized analogues, containing a naphthalene or phenyl-triazolyl scaffold were compared in a mouse model of chronic neuropathic pain (sciatic constriction). P2Y14R antagonists rapidly (≤30 min) reversed mechano-allodynia, with maximal effects typically within 1 h after injection. Two analogues (4-[4-(4-piperidinyl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthalenecarboxylic acid 1 and N-acetyl analogue 4</ ...[more]

PMID: 32551012

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Dataset Information

P2Y₁₄ Receptor Antagonists Reverse Chronic Neuropathic Pain in a Mouse Model.

Publications

P2Y<sub>14</sub> Receptor Antagonists Reverse Chronic Neuropathic Pain in a Mouse Model.

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