TCN 238

TCN 238 is an orally bioavailable positive allosteric modulator of the metabotropic glutamate receptor 4 (mGluR4; EC₅₀ = 1 µM).¹ It has a greater than 30-fold selectivity for mGluR4 over mGluR5 using human recombinant receptors in CHO-K1 cells. It has no activity at the adenosine A_2A, serotonin 5-HT_1A, or α_2A-adrenergic receptors at concentrations up to 10 µM. In a haloperidol-induced catalepsy rat model of Parkinson’s disease, it dose-dependently reduces catalepsy with an ED₅₀ of approximately 1 mg/kg. TCN 238 administration in rats leads to downregulation of the mGluR4 gene, GRM4, in the hippocampus and the gene for the GABA_A receptor α subunit, GABRA1, in the frontal cortex without affecting hippocampal-dependent memory.²

WARNING This product is not for human or veterinary use.

1. East, S.P., Bamford, S.J., Dietz, M.G.A., et al. An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction. Bioorg. Med. Chem. Lett. 20(16), 4901-4905 (2010).

2. Pershina, E.V., and Arkhipov, V.I. Subacute activation of mGlu4 receptors causes the feedback inhibition of its gene expression in rat brain. Life Sci. 153, 50-54 (2016).