Angeli Andrea, Vaiano Fabio, Mari Francesco, Bertol Elisabetta, Supuran Claudiu T
a Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.
b Forensic Toxicology Division, Department of Health Sciences , University of Florence , Florence , Italy.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):1253-1259. doi: 10.1080/14756366.2017.1375485.
Identifying possible new biological activities of psychoactive substances belonging to various chemical classes may lead to a better understanding of their mode of action and side effects. We report here that amines structurally related to amphetamine, a widely used psychoactive substance, such as amphetamine, methamphetamine, phentermine, mephentermine, and chlorphenteramine, potently activate several carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in important physiological functions. Of the 11 investigated human (h) isoforms, the widespread hCA I and II, the secreted hCA VI, as well as the cytosolic hCA XIII, and membrane-bound hCA IX and XIV were poorly activated by these amines, whereas the extracellular hCA IV, the mitochondrial enzymes hCA VA/VB, the cytosolic hCA VII, and the transmembrane isoform hCA XII were potently activated. Some of these enzymes are abundant in the brain, raising the possibility that some of the cognitive effects of such psychoactive substances might be related to their activation of these enzymes.
确定属于不同化学类别的精神活性物质可能存在的新生物活性，有助于更好地理解其作用方式和副作用。我们在此报告，与广泛使用的精神活性物质苯丙胺结构相关的胺类，如苯丙胺、甲基苯丙胺、芬特明、美芬丁胺和氯苯丁胺，能有效激活几种参与重要生理功能的碳酸酐酶（CA，EC 4.2.1.1）同工型。在所研究的11种人类（h）同工型中，广泛存在的hCA I和II、分泌型hCA VI、胞质型hCA XIII以及膜结合型hCA IX和XIV被这些胺类激活的程度较低，而细胞外hCA IV、线粒体酶hCA VA/VB、胞质型hCA VII以及跨膜同工型hCA XII则被有效激活。其中一些酶在大脑中含量丰富，这增加了此类精神活性物质的某些认知效应可能与其对这些酶的激活有关的可能性。
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