L-trans-Pyrrolidine-2,4-dicarboxylic acid

L-trans-Pyrrolidine-2,4-dicarboxylic acid (L-trans-2,4-PDC) is an inhibitor of L-glutamate transport (Ki = 4.6 μM in rat brain synaptosomes). It inhibits radioligand binding to NMDA receptors by 13% but has no effect on AMPA or kainate receptors when used at a concentration of 100 μM. L-trans-2,4-PDC is neurotoxic to astrocyte-rich and astrocyte-poor rat cortical cultures (EC50s = 320 and 50 μM, respectively), an effect that can be reversed by the NMDA antagonist MK-801 and glutamate-pyruvate transaminase but not the non-NMDA glutamate receptor antagonist CNQX. It induces efflux of the non-metabolizable glutamate analog [3H]-D-aspartate in an extracellular sodium-dependent manner. In vivo, L-trans-2,4-PDC (0.05-0.2 μg/side) prevents amphetamine-induced hyperlocomotion in a dose-dependent manner in rats when injected directly into the nucleus accumbens. It also increases bladder intercontraction interval (ICI) without affecting postvoid residual or basal pressure in rats.

L-trans-Pyrrolidine-2,4-dicarboxylic Acid is an inhibitor of the glutamate transporter EAAT.

Potent, competitive, transportable EAAT1-4 inhibitor/non-transportable EAAT5 inhibitor. Also available as part of the Excitatory Amino Acid Transporter Inhibitor Tocriset™ .

Store at RT

[1] RICHARD J. BRIDGES. Conformationally defined neurotransmitter analogs. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer[J]. Journal of Medicinal Chemistry, 1991, 34 2: 717-725. DOI:10.1021/jm00106a037.
[2] Blitzblau, R., Gupta, S., Djali, S., et al. The glutamate transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylate indirectly evokes NMDA receptor mediated neurotoxicity in rat cortical cultures. Eur. J. Neurosci. 8(9), 1840-1852 (1996).
[3] David, H.N., Thévenoux, A., and Abraini, J.H. Inhibition of the glutamate transporter by L-trans-PDC in the nucleus accumbens prevents the locomotor response to amphetamine. Neuropharmacology 41(3), 409-411 (2001).
[4] MASASHI HONDA. Supraspinal and spinal effects of L-trans-PDC, an inhibitor of glutamate transporter, on the micturition reflex in rats.[J]. Neurourology and Urodynamics, 2013, 32 7: 1026-1030. DOI:10.1002/nau.22351.