Pliashkevich Iu G, Barsegian G G, Kisileva N I, Rusakov D Iu, Rozhanets V V, Dement'eva I G, Pliashkevich N A
Eksp Klin Farmakol. 2005 Mar-Apr;68(2):11-4.
Adducts obtained via the interaction of formaldehyde with histidine (1,2,3,4-tetrahydroimidazo[4, 5-c]pyridine-3-carboxylic acid (I)), tyrosine (7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (II)), and dopamine (6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (III)) influence the behavior and the state of the brain receptor system of rats upon chronic administration (10-day treatment at a daily dose of 50 mg/kg, i.p.). All the compounds studied decrease the horizontal and (to a lower extent) vertical motor activity and increase the quiescence period duration. On the other hand, the effects of compounds tested on the vegetative reactions were different: compounds I and III increased, whereas compound II decreased these reactions. Using the radioligand binding method, it was established that the treatment with compound I led to a decrease in the density of benzodiazepine receptors (B max of [3H]-flunitrazepam was 78% of the control level) and to a significant (148%) increase in the density of specific binding sites for [3H]-spiperone (reflecting the total density of dopamine (D2) and serotonin (5-HT2) receptors. The chronic administration of compound III produced a reliable decrease (76% of the control level) only in the density of benzodiazepine receptors. None of the tested compounds influenced the affinity of receptors with respect to the radioactive ligands used.
通过甲醛与组氨酸(1,2,3,4 - 四氢咪唑并[4,5 - c]吡啶 - 3 - 羧酸(I))、酪氨酸(7 - 羟基 - 1,2,3,4 - 四氢异喹啉 - 3 - 羧酸(II))和多巴胺(6,7 - 二羟基 - 1,2,3,4 - 四氢异喹啉(III))相互作用获得的加合物,在长期给药(每天腹腔注射剂量为50 mg/kg,持续10天)后会影响大鼠的行为和大脑受体系统状态。所有研究的化合物均会降低水平运动活性以及(程度较低地)垂直运动活性,并延长静止期持续时间。另一方面,所测试化合物对植物性反应的影响有所不同:化合物I和III会增强这些反应,而化合物II则会减弱这些反应。采用放射性配体结合法确定,用化合物I处理会导致苯二氮䓬受体密度降低([³H] - 氟硝西泮的Bmax为对照水平的78%),并使[³H] - 螺哌隆特异性结合位点的密度显著增加(148%,反映多巴胺(D2)和5 - 羟色胺(5 - HT2)受体的总密度)。长期给予化合物III仅使苯二氮䓬受体密度可靠地降低(为对照水平的76%)。所测试的化合物均未影响受体对所用放射性配体的亲和力。