P2Y14 Receptor Antagonists Reverse Chronic Neuropathic Pain in a Mouse Model

Title
P2Y14 Receptor Antagonists Reverse Chronic Neuropathic Pain in a Mouse Model
Authors
유진하Fatma MuftiYoung-Hwan JungLuigino Antonio GiancottiZhoumou ChenNgan B. PhungKenneth A. JacobsonDaniela Salvemini
Issue Date
2020-04
Publisher
ACS MEDICINAL CHEMISTRY LETTERS
Citation
VOL 4, NO 6-1286
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.
URI
http://pubs.kist.re.kr/handle/201004/72203
ISSN
1948-5875
Appears in Collections:
KIST Publication > Article
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