Dipraglurant is a promising compound that acts as a negative allosteric modulator (NAM) of the metabotropic glutamate receptor type 5 (mGluR5). It has shown potential for the treatment of neurological diseases, particularly in reducing levodopa-induced dyskinesia (LID) in Parkinson’s disease.

Dipraglurant is a potent, selective, orally active and brain penetrant mGluR5 negative allosteric modulator.

Dipraglurant (ADX48621) is a potent and selective mGluR5 NAM, with an IC50 of 21 nM. It is orally active, allowing for convenient administration. Besides, Dipraglurant can penetrate the blood-brain barrier, enabling it to act directly on the central nervous system. Furthermore, in preclinical studies using parkinsonian primates, dipraglurant demonstrated dose-dependent efficacy in reducing both choreic and dystonic LID induced by levodopa.

Dipraglurant can counteract abnormal membrane responses and calcium rise induced by D2 receptor agonists or caged dopamine. In macaque models, a single oral dose of dipraglurant (3-30 mg/kg) effectively reduced levodopa-induced chorea and dystonia without interfering with the efficacy of levodopa in treating parkinsonian disability. Dipraglurant exhibits favorable pharmacokinetic properties, with maximum plasma concentrations (Cmax) and area under the curve (AUCinf) following oral administration in macaques.

In conclusion, dipraglurant is an orally active mGluR5 NAM that shows promise for the treatment of neurological diseases, particularly in reducing levodopa-induced dyskinesia.

References:

[1] Mellone M, et al. 2018 Aug;125(8):1225-1236.

[2] Sciamanna G, et al. Neuropharmacology. 2014 Oct;85:440-50.