Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication. Drug-free patients show 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 show 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 effects of conventional anti-PD drugs. Atremorine also influences the levels of other neurotransmitters (adrenaline, noradrenaline) and hormones which are regulated by DA (e.g., prolactin, PRL), with no effect on serotonin or histamine. The variability in Atremorine-induced DA response is highly attributable to pharmacogenetic factors. Polymorphic variants in pathogenic (SNCA, NUCKS1, ITGA8, GPNMB, GCH1, BCKDK, APOE, LRRK2, ACMSD), mechanistic (DRD2), metabolic (CYP2D6, CYP2C9, CYP2C19, CYP3A4/5, NAT2), transporter (ABCB1, SLC6A2, SLC6A3, SLC6A4) and pleiotropic genes (APOE) influence the DA response to Atremorine and its psychomotor and brain effects. Atremorine enhances DNA methylation and displays epigenetic activity via modulation of the pharmacoepigenetic network. Atremorine is a novel neuroprotective agent for dopaminergic neurons with potential prophylactic and therapeutic activity in PD.

中文翻译：

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帕金森病中的心绞痛：从多巴胺能神经保护到药物基因组学

Atremorine 是一种新型生物产品，通过非变性生物技术过程从蚕豆遗传物种中获得. Atremorine 是一种有效的多巴胺 (DA) 增强剂，对神经元多巴胺能系统具有强大的作用，可作为帕金森病 (PD) 的神经保护剂。超过 97% 的 PD 患者在给药后 1 小时对单剂量的 Atremorine (5 g, po) 有反应。这种反应与性别、时间、剂量和基因型有关，最佳剂量范围为 5 至 20 克/天，具体取决于疾病严重程度和伴随用药。无药物患者的 DA 水平从 12.14 ± 0.34 pg/ml 增加到 6463.21 ± 1306.90 pg/ml；长期接受抗 PD 药物治疗的患者的 DA 水平从 1321.53 ± 389.94 pg/ml 增加到 16,028.54 ± 4783.98 pg/ml，表明 Atremorine 增强了常规抗 PD 药物的多巴胺能作用。Atremorine 还影响其他神经递质（肾上腺素、去甲肾上腺素）和受 DA 调节的激素（例如催乳素、PRL），对血清素或组胺没有影响。Atremorine 诱导的 DA 反应的变异性高度归因于药物遗传因素。致病性多态性变异（SNCA、NUCKS1、ITGA8、GPNMB、GCH1、BCKDK、APOE、LRRK2、ACMSD）、机械（DRD2）、代谢（CYP2D6、CYP2C9、CYP2C19、CYP3A4/5、NAT2）、转运蛋白（ABCB1、SLC6A4A2）和SLC6A4A2多效性基因 ( APOE ) 影响 DA 对 Atremorine 的反应及其精神运动和大脑效应。Atremorine 通过调节药物表观遗传网络增强 DNA 甲基化并显示表观遗传活性。Atremorine 是一种新型的多巴胺能神经元神经保护剂，在 PD 中具有潜在的预防和治疗活性。