Jones, Carrie K.’s team published research in Journal of Pharmacology and Experimental Therapeutics in 340 | CAS: 377727-87-2

Jones, Carrie K. published the artcileThe metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson’s disease, Product Details of C25H29N9O3, the publication is Journal of Pharmacology and Experimental Therapeutics (2012), 340(2), 404-421, database is CAplus and MEDLINE.

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder associated with severe motor impairments caused by the loss of dopaminergic innervation of the striatum. Previous studies have demonstrated that pos. allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu₄), including N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide, can produce antiparkinsonian-like effects in preclin. models of PD. However, these early mGlu₄ PAMs exhibited unsuitable physiochem. properties for systemic dosing, requiring intracerebroventricular administration and limiting their broader utility as in vivo tools to further understand the role of mGlu₄ in the modulation of basal ganglia function relevant to PD. In the present study, we describe the pharmacol. characterization of a systemically active mGlu₄ PAM, N-(3-chlorophenyl)picolinamide (VU0364770), in several rodent PD models. VU0364770 showed efficacy alone or when administered in combination with L-DOPA or an adenosine 2A (A_2A) receptor antagonist currently in clin. development (preladenant). When administered alone, VU0364770 exhibited efficacy in reversing haloperidol-induced catalepsy, forelimb asymmetry-induced by unilateral 6-hydroxydopamine (6-OHDA) lesions of the median forebrain bundle, and attentional deficits induced by bilateral 6-OHDA nigrostriatal lesions in rats. In addition, VU0364770 enhanced the efficacy of preladenant to reverse haloperidol-induced catalepsy when given in combination. The effects of VU0364770 to reverse forelimb asymmetry were also potentiated when the compound was coadministered with an inactive dose of L-DOPA, suggesting that mGlu₄ PAMs may provide L-DOPA-sparing activity. The present findings provide exciting support for the potential role of selective mGlu₄ PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either L-DOPA or A_2A antagonists.

Journal of Pharmacology and Experimental Therapeutics published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C25H29N9O3, Product Details of C25H29N9O3.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics