Selective metabotropic glutamate receptor 2 positive allosteric modulation alleviates L-DOPA-induced psychosis-like behaviours and dyskinesia in the MPTP-lesioned marmoset.

Selective metabotropic glutamate receptor 2 positive allosteric modulation alleviates L-DOPA-induced psychosis-like behaviours and dyskinesia in the MPTP-lesioned marmoset. Eur J Pharmacol. 2020 Jan 28;:172957 Authors: Sid-Otmane L, Hamadjida A, Nuara SG, Bédard D, Gaudette F, Gourdon JC, Michaud V, Beaudry F, Panisset M, Huot P Abstract Psychosis and dyskinesia significantly diminish the quality of life of patients with advanced Parkinson's disease (PD). Available treatment options are unfortunately few and their use is limited by adverse effects. We have recently shown that activation of metabotropic glutamate 2 and 3 (mGlu2/3) receptors produced significant relief of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced psychosis-like behaviours (PLBs) and dyskinesia in experimental models of PD. Here, using the highly-selective mGlu2 positive allosteric modulator (PAM) LY-487,379, we seek to determine the contribution of selective mGlu2 activation on both L-DOPA-induced PLBs and dyskinesia, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. We first determined the pharmacokinetic (PK) profile of LY-487,379 in the common marmoset, following which we administered it (0.1, 1 and 10 mg/kg) or its vehicle to 6 MPTP-lesioned marmosets previously exposed to L-DOPA to elicit stable PLBs and dyskinesia. We found that LY-487,379 provided a ≈45% reduction of the global PLBs observed and reduced global dyskinesia score...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research