Influence of dopamine, noradrenaline, and serotonin transporters on the pharmacogenetics of Atremorine in Parkinson's disease. Issue 5 (17th January 2021)

• Record Type: Journal Article
• Authors: Cacabelos, Ramón; Carrera, Iván; Martínez, Olaia; Naidoo, Vinogran; Cacabelos, Natalia; Aliev, Gjumrakch; Carril, Juan C.
• Other Names: Squassina Alessio guestEditor.
• Is Part Of: Drug development research. Volume 82:Issue 5(2021)
• Page Start: 695
• Page End: 706
• Publication Date: 2021-01-17
• Subjects: Atremorine -- neurotransmitter transporter genes -- Parkinson's disease; Drug development -- Periodicals; Drugs -- Research -- Periodicals; 615.19
• DOI: 10.1002/ddr.21784
• Languages: English
• ISSNs: 0272-4391

Abstract

Abstract: Atremorine is a potent dopamine (DA) enhancer obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba . Atremorine affects the neuronal dopaminergic system by acting as a neuroprotective agent against Parkinson's disease (PD). PD patients (N = 127) responded to a single dose of Atremorine (5 g, p.o.) 1 h after administration in a sex‐, time‐, dose‐, and genotype‐dependent fashion. Drug‐free patients (N = 81) showed an increase in DA levels from 12.14 ± 0.34 pg/ml to 6463.21 ± 1306.90 pg/ml; and patients chronically treated with anti‐PD drugs (N = 46) showed an increase in DA levels from 1321.53 ± 389.94 pg/ml to 16, 028.54 ± 4783.98 pg/ml, indicating that Atremorine potentiates the dopaminergic effect of conventional anti‐PD drugs. The variability in Atremorine‐induced DA response is strongly attributable to pharmacogenetic factors. Polymorphic variants in pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes influence the DA response to Atremorine. Genetic variation in the DA ( SLC6A3; rs460000 ), noradrenaline (NA) ( SLC6A2; rs12708954, rs3785143, rs5569 ), and serotonin (5‐HT) transporter ( SLC6A4; rs2020934, rs2020936, rs4251417, rs6354 ) genes exert a genotype‐dependent Atremorine‐induced DA response in PD, with potential impact on the DA‐related pharmacogenetic outcome and minimum effects on NA and 5‐HT levels.