SYM 2081

SYM 2081 is an agonist of the kainate receptor.¹ It induces currents in Xenopus oocytes expressing homomeric GluK1 or GluK5 subunit-containing receptors (EC₅₀s = 0.16 and 0.23 µM, respectively). It induces desensitization in HEK293 cells expressing homomeric GluK2 subunit-containing kainate receptors when used at concentrations ranging from 0.03 to 0.3 µM.² SYM 2081 selectively binds to the kainate receptor (IC₅₀ = ~0.035 µM) over the AMPA and NMDA receptors (IC₅₀s = >100 and 7 µM, respectively) but does bind to excitatory amino acid transporter 2 (EAAT2; K_b = 3.4 µM) and inhibits glutamate transport.^3,4 In vivo, SYM 2081 (10, 50, and 100 mg/kg, i.p.) reduces hind paw withdrawal frequency and increases withdrawal latency to mechanical and thermal stimuli in a rat model of hyperalgesia induced by the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin (Item Nos. 92350 | 10010743).⁵

WARNING This product is not for human or veterinary use.

1. Donevan, S.D., Beg, A., Gunther, J.M., et al. The methylglutamate, SYM 2081, is a potent and highly selective agonist at kainate receptors. J. Pharmacol. Exp. Ther. 285(2), 539-545 (1998).

2. Zhou, L.M., Gu, Z.Q., Costa, A.M., et al. (2S,4R)-4-methylglutamic acid (SYM 2081): A selective, high-affinity ligand for kainate receptors. J. Pharmacol. Exp. Ther. 280(1), 422-427 (1997).

3. Gu, Z.Q., Hesson, D.P., Pelletier, J.C., et al. Synthesis, resolution, and biological evaluation of the four stereoisomers of 4-methylglutamic acid: Selective probes of kainate receptors. J. Med. Chem. 38(14), 2518-2520 (1995).

4. Vandenberg, R.J., Mitrovic, A.D., Chebib, M., et al. Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2. Mol. Pharmacol. 51(5), 809-815 (1997).

5. Turner, S.S., Hamamoto, D.T., Hodges, J.S., et al. SYM 2081, an agonist that desensitizes kainate receptors, attenuates capsaicin and inflammatory hyperalgesia. Brain Res. 973(2), 252-264 (2003).