MPEP HCl (219911-35-0) is a potent (IC50 = 36 nM for quisqualate-stimulated phosphoinositide hydrolysis) and selective (over mGlu1b, -2, -3, -4a, -6, -7b, and -8a) antagonist of the metabotropic glutamate receptor subtype 5 (mGlu5).1 It is a positive allosteric modulator of human mGlu4.2 MPEP inhibition of mGlu5 has been studied for the treatment of many CNS disorders including Parkinson’s3,4, Fragile X syndrome5, and addiction6.
1) Gasparini et al. (1999) 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective, and systemically active mGlu5 receptor antagonist; Neuropharmacology 38 1493
2) Mathiesen et al. (2003) Positive allosteric modulation of the human metabotropic glutamate receptor 4(hmGlu4) by SIB-1893 and MPEP; Br. J . Pharmacol. 138 1026
3) Morin et al. (2010) Effect of metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys; Neuropharmacology 58 981
4) Morin et al. (2013) MPEP, an mGlu5 receptor antagonist, reduces the development of L-DOPA-induced motor complications in de novo parkinsonian monkeys: biochemical correlates; Neuropharmacology 66 355
5) Michalon et al. (2012) Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice; Neuron 74 49
6) Mihov and Hasler (2016) Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window; Int. J. Neuropsychopharmacol. 19 pyw002