Kulikov A V, Tikhonova M A, Kulikova E A, Khomenko T M, Korchagina D V, Volcho K P, Salachutdinov H F, Popova N K
Mol Biol (Mosk). 2011 Mar-Apr;45(2):282-8.
Study of molecular mechanisms of psychotropic drug action is the main aim of molecular psychopharmacology. New synthetic analog of variacin 8-(Trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine (TX-2153) was shown to produce anxiolytic and anticonvulsant effects on mice. Here the effect of chronic administration of TX-2153 on expression of some serotonin-related genes in mouse brain was investigated. The drug (10 mg/kg, per os, 16 days) was administered to adult males of ASC (Antidepressant Sensitive Catalepsy) mouse strain characterizing by alterations in behavior and brain serotonin system. The expression of genes encoding 1) the key enzyme of serotonin synthesis, tryptophan hydroxylase 2 (TPH2), 2) main enzyme of serotonin degradation, monoamine oxydase A (MAOA), 3) 5-HT transporter (SERT) and 4) 5-HT(1A) receptor was studied using quantitative RT-PCR. TX-2153 significantly reduced m-RNA level of 5-HT(1A) receptor and MAOA genes in the midbrain without any effect on expression of these genes in the frontal cortex and hippocampus. The drug failed to affect expression of TPH2 and SERT genes in the midbrain. The result indicates involvement of the brain 5-HT system in the molecular mechanism underlying the effect of TX-2153.
精神药物作用分子机制的研究是分子精神药理学的主要目标。新型合成变种霉素类似物8-（三氟甲基）-1,2,3,4,5-苯并五硫杂环庚烷-6-胺（TX-2153）对小鼠具有抗焦虑和抗惊厥作用。本文研究了长期给予TX-2153对小鼠脑中一些血清素相关基因表达的影响。将该药物（10mg/kg，口服，16天）给予ASC（抗抑郁药敏感僵住症）小鼠品系的成年雄性小鼠，该品系具有行为和脑血清素系统改变的特征。使用定量RT-PCR研究了编码1）血清素合成关键酶色氨酸羟化酶2（TPH2）、2）血清素降解主要酶单胺氧化酶A（MAOA）、3）5-羟色胺转运体（SERT）和4）5-羟色胺（1A）受体的基因表达。TX-2153显著降低了中脑中5-羟色胺（1A）受体和MAOA基因的mRNA水平，而对额叶皮质和海马体中这些基因的表达没有影响。该药物未能影响中脑中TPH2和SERT基因的表达。结果表明脑5-羟色胺系统参与了TX-2153作用的分子机制。
