Pinna, Annalisa published the artcileNeuroinflammation and L-dopa-induced abnormal involuntary movements in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease are counteracted by combined administration of a 5-HT1A/1B receptor agonist and A2A receptor antagonist, Quality Control of 377727-87-2, the publication is Neuropharmacology (2021), 108693, database is CAplus and MEDLINE.
Several lines of evidence have strongly implicated neuroinflammation in Parkinson’s disease (PD) progression and L-dopa-induced dyskinesia. The present study investigated whether early subchronic pretreatment with the serotonin 5-HT1A/1B receptor agonist eltoprazine plus the adenosine A2A receptor antagonist preladenant counteracted L-dopa-induced abnormal involuntary movements (AIMs, index of dyskinesia), and neuroinflammation, in unilateral 6-hydroxydopamine(6-OHDA)-lesioned rat model of PD. The immunoreactivity of glial fibrillary acidic protein (GFAP), and the colocalization of ionized calcium binding adaptor mol.-1 (IBA-1), with interleukin (IL)-1β, tumor-necrosis-factor-αF (TNF-α) and IL-10 were evaluated in the denervated caudate-putamen (CPu) and substantia nigra pars-compacta (SNc). The combined subchronic pretreatment with L-dopa plus eltoprazine and preladenant reduced AIMs induced by acute L-dopa challenge in these rats and decreased GFAP and IBA-1 immunoreactivity induced by the drug in both CPu and SNc, with reduction in IL-1β in IBA-1-pos. cells in both CPu and SNc, and in TNF-α in IBA-1-pos. cells in SNc. Moreover, a significant increase in IL-10 in IBA-1-pos. cells was observed in SNc. Evaluation of immediate early-gene zif-268 (index of neuronal activation) after L-dopa challenge, showed an increase in its expression in denervated CPu of rats pretreated with L-dopa or L-dopa plus preladenant compared with vehicle, whereas rats pretreated with eltoprazine, with or without preladenant, had lower zif-268 expression. Finally, tyrosine hydroxylase and dopamine transporter examined to evaluate neurodegeneration, showed a significant equal decrease in all exptl. groups. The present findings suggest that combination of L-dopa with eltoprazine and preladenant may be promising therapeutic strategy for delaying the onset of dyskinesia, preserving L-dopa efficacy and reducing neuroinflammation markers in nigrostriatal system of 6-OHDA-lesioned rats.
Neuropharmacology 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, Quality Control of 377727-87-2.
Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics