(S)-3,4-DCPG

(S)-3,4-DCPG ((S)-3,4-Dicarboxyphenylglycine) is a potent and selective mGlu8a receptor agonist with an EC₅₀ of 31 nM for human mGlu8a. (S)-3,4-DCPG inhibits Forskolin (HY-15371)-stimulated cAMP formation by activating mGlu8, and modulates presynaptic glutamatergic transmission and synaptic plasticity. (S)-3,4-DCPG can be used in research on inflammatory pain, neuropathic pain, autism spectrum disorder, and glutamatergic synaptic plasticity^[1][2][3]. In Vitro:(S)-3,4-DCPG ((S)-3,4-Dicarboxyphenylglycine) (≤ 100 μM) selectively activates mGlu8a in RGT (AV12-664) cells expressing human mGlu1-8, and inhibits forskolin-stimulated cAMP formation. It has an EC₅₀ of 31 nM for mGlu8a, while the EC50 values for mGlu4a, mGlu6 and mGlu7a are 8.8 μM, 3.6 μM and > 100 μM, respectively, demonstrating its selectivity for mGlu8a^[1].
(S)-3,4-DCPG (0.5-400 μM; 5 min) inhibits the fast component of dorsal root-evoked ventral root potential (fDR-VRP) in spinal cord preparations from neonatal rats, producing a biphasic concentration-response curve. The EC₅₀ values of the high-affinity and low-affinity components are 1.3 μM and 391 μM, respectively, with the high-affinity component mainly mediated by mGlu8^[1]. In Vivo:(S)-3,4-DCPG ((S)-3,4-Dicarboxyphenylglycine) (10, 30, or 60 mg/kg; 15 min before formalin administration; i.p.) dose-dependently reduces both early and late nociceptive responses in the formalin-induced inflammatory pain model of male Swiss-Webster mice, and the effect of 60 mg/kg is blocked by MSOP, a Group III metabotropic glutamate receptor antagonist administered into the PAG^[2].
(S)-3,4-DCPG (30 or 60 mg/kg; 15 min prior to carrageenan; i.p.) increases the thermal withdrawal latency and mechanical withdrawal threshold in the carrageenan (HY-125474) inflammatory pain model, whereas administration of (S)-3,4-DCPG at 1 h after carrageenan treatment exerts no significant effect^[2].
(S)-3,4-DCPG (60 mg/kg; single dose; i.p.) increases paw withdrawal latency to heat and mechanical paw withdrawal threshold on day 3 after chronic constriction injury of the sciatic nerve, thereby alleviating thermal hyperalgesia and mechanical allodynia, but exerts no significant effect on day 7 post-injury^[2].
(S)-3,4-DCPG (1 μM/0.5 μL per side; intra-DG) reverses the reduced social novelty preference index (SNPI) in prenatal VPA-induced Wistar rat models of autism, and enhances fEPSP LTP in the PP-DG pathway of VPA-exposed rats, while inhibiting LTP in normal control rats^[3].