Departamento de Fisicoquímica, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior SN, Ciudad Universitaria, CP 04510, Ciudad de México, CDMX, Mexico.
Departamento Académico de Ingeniería Industrial y Operaciones, Instituto Tecnológico Autónomo de México, Río, Hondo 1, Altavista, Álvaro Obregón, CP 01080, Ciudad de México, CDMX, Mexico.
Sci Rep. 2020 Dec 9;10(1):21581. doi: 10.1038/s41598-020-78446-4.
Dopamine is an important neurotransmitter that plays a key role in a wide range of both locomotive and cognitive functions in humans. Disturbances on the dopaminergic system cause, among others, psychosis, Parkinson's disease and Huntington's disease. Antipsychotics are drugs that interact primarily with the dopamine receptors and are thus important for the control of psychosis and related disorders. These drugs function as agonists or antagonists and are classified as such in the literature. However, there is still much to learn about the underlying mechanism of action of these drugs. The goal of this investigation is to analyze the intrinsic chemical reactivity, more specifically, the electron donor-acceptor capacity of 217 molecules used as dopaminergic substances, particularly focusing on drugs used to treat psychosis. We analyzed 86 molecules categorized as agonists and 131 molecules classified as antagonists, applying Density Functional Theory calculations. Results show that most of the agonists are electron donors, as is dopamine, whereas most of the antagonists are electron acceptors. Therefore, a new characterization based on the electron transfer capacity is proposed in this study. This new classification can guide the clinical decision-making process based on the physiopathological knowledge of the dopaminergic diseases.
多巴胺是一种重要的神经递质,在人类的运动和认知功能中起着关键作用。多巴胺系统的紊乱会导致精神分裂症、帕金森病和亨廷顿病等疾病。抗精神病药主要与多巴胺受体相互作用,因此对于控制精神分裂症和相关疾病非常重要。这些药物作为激动剂或拮抗剂发挥作用,并在文献中进行了分类。然而,关于这些药物的作用机制仍有许多需要了解。本研究的目的是分析 217 种作为多巴胺物质使用的分子的固有化学反应性,更具体地说,是电子供体-受体能力,特别关注用于治疗精神分裂症的药物。我们应用密度泛函理论计算分析了 86 种被归类为激动剂的分子和 131 种被归类为拮抗剂的分子。结果表明,大多数激动剂是电子供体,就像多巴胺一样,而大多数拮抗剂是电子受体。因此,本研究提出了一种基于电子转移能力的新表征。这种新的分类可以根据多巴胺疾病的生理病理学知识指导临床决策过程。