Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation
Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation
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DOI：
10.3109/1061186x.2015.1035275
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发表时间：
2015-01-01
影响因子：
4.5
通讯作者：
Giannola, Libero Italo
中科院分区：
文献类型：
--
作者：
De Caro, Viviana;Sutera, Flavia Maria;Giannola, Libero Italo
2-氨基-N-[2-（3，4-二羟基-苯基）-乙基]-3-苯基-丙酰胺（DA-PHEN）已被合成以获得能够将多巴胺（DA）释放到CNS中的潜在前药。然而，DA-PHEN本身可以作为多巴胺能药物。在本研究中，通过平行人工渗透性测定（PAMPA）获得的渗透性转运（P-e）表明被动跨细胞转运较低（P-e = 0.32 +/- 0.01 x 10（-6）cm/s）。使用Caco-2细胞系统，吸收方向的P-app（AP-BL）（3.36 +/- 0.02 x 10（-5）cm/s）显著高于分泌方向的Papp BL-AP（1.75 +/- 0.07 x 10（-5）cm/s），表明存在极化转运。外排率（P-app（AP-BL）/P-app（BL-AP）= 0.52 +/- 0.02）表明DA-PHEN对外排载体的亲和力较低。强迫游泳测试强调了在测试前和测试期间不动时间的减少（p
2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-PHEN) has been previously synthesized to obtain a potential prodrug capable of release dopamine (DA) into CNS. However, DA-PHEN could act per se as a dopaminergic drug. In this study, the permeability transport (P-e), obtained by parallel artificial permeability assay (PAMPA), indicated a low passive transcellular transport (P-e = 0.32 +/- 0.01 x 10(-6) cm/s). Using the Caco-2 cell system, the P-app (AP-BL) in absorptive direction (3.36 +/- 0.02 x 10(-5) cm/s) was significantly higher than the Papp BL-AP in secretive direction (1.75 +/- 0.07 x 10(-5) cm/s), suggesting a polarized transport. The efflux ratio (P-app (AP-BL)/P-app (BL-AP) = 0.52 +/- 0.02) indicated a low affinity of DA-PHEN to efflux carriers. The forced swim test highlighted a reduction of immobility time in both pre-test and test sessions (p