L-DOPA ESTERS AS POTENTIAL PRODRUGS .4. EFFECT ON BRAIN CONCENTRATION OF DOPAMINE METABOLITES IN RESERPINIZED MICE
L-DOPA ESTERS AS POTENTIAL PRODRUGS .4. EFFECT ON BRAIN CONCENTRATION OF DOPAMINE METABOLITES IN RESERPINIZED MICE
复制标题
DOI：
10.1111/j.2042-7158.1987.tb05123.x
复制
发表时间：
1987-10-01
影响因子：
3.3
通讯作者：
MARSDEN, CD
中科院分区：
文献类型：
--
作者：
COOPER, DR;MARREL, C;MARSDEN, CD
腹腔注射左旋多巴和左旋多巴的一系列酯类前体药物给利血平化的小鼠产生纹状体和嗅结节高香草酸（HVA）和3，4-二羟基苯乙酸（DOPAC）水平升高。与左旋多巴相比，个别药物产生的变化模式存在差异。只有苯氧乙酯引起纹状体和嗅结节HVA和DOPAC的升高，大于L-多巴给药后测得的值。总体而言，间三氟甲基苄基，苯乙基，对氯苯乙基和对甲氧基苯乙基酯前药产生更大的海拔纹状体和嗅结节HVA，但不是DOPAC，与L-多巴。施用2-四氢吡喃基甲基衍生物仅增强纹状体HVA，并且2-羟丙基、正丙基、甲基、乙基和2-（1-甲氧基）丙基酯前药的纹状体和嗅结节DOPAC浓度与施用L-多巴本身产生的浓度相当。观察到的纹状体和嗅结节HVA和DOPAC水平的变化与这些化合物引起利血平小鼠自发活动的能力无关。
The intraperitoneal administration of L-dopa and a series of ester prodrugs of L-dopa to reserpinized mice produced elevations of striatal and tuberculum olfactorium homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Differences, in the pattern of change produced by individual drugs, compared with L-dopa, were observed. Only the phenoxyethyl ester caused elevations of both striatal and tuberculum olfactorium HVA and DOPAC, greater than those measured following L-dopa administration. Overall the m-trifluoromethylbenzyl, phenylethyl, p-chlorophenylethyl and p-methoxyphenylethyl ester prodrugs produced greater elevations of striatal and tuberculum olfactorium HVA, but not DOPAC, compared with L-dopa. The administration of the 2-tetrahydropyranylmethyl derivative only enhanced striatal HVA and striatal and tuberculum olfactorium DOPAC concentration of the 2-hydroxypropyl, n-propyl, methyl, ethyl and 2-(1-methoxy)propyl ester prodrugs were comparable with those produced by the administration of L-dopa itself. The alterations in striatal and tuberculum olfactorium HVA and DOPAC levels observed did not correlate with the ability of these compounds to elicit locomotor activity in reserpinized mice.