Fuller R W, Hemrick-Luecke S K
Res Commun Chem Pathol Pharmacol. 1986 Aug;53(2):167-72.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused marked depletion of dopamine and of its two metabolites, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid) one week after the last of four daily s.c. injections (20 mg/kg) in mice. Norepinephrine concentration in the frontal cortex was also decreased. m-Hydroxy-MPTP at a higher dose (80 mg/kg s.c.) caused a similar degree of depletion of dopamine and its metabolites in striatum and of norepinephrine in frontal cortex. p-Hydroxy-MPTP and o-hydroxy-MPTP (both at 80 mg/kg s.c.) caused no significant change in striatal dopamine or in cortical norepinephrine concentrations and had little or no effect on the dopamine metabolites. The m-hydroxy analog increases the list of MPTP-like compounds known to cause persistent depletion of striatal dopamine, and the positional isomers of this compound illustrate the strict structural dependency of this effect.
在对小鼠进行连续四天每日皮下注射（20毫克/千克）1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）后一周，多巴胺及其两种代谢产物3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）显著减少。额叶皮质中的去甲肾上腺素浓度也降低。较高剂量（80毫克/千克皮下注射）的间羟基-MPTP在纹状体中引起的多巴胺及其代谢产物的减少程度与在额叶皮质中引起的去甲肾上腺素减少程度相似。对羟基-MPTP和邻羟基-MPTP（均为80毫克/千克皮下注射）对纹状体多巴胺或皮质去甲肾上腺素浓度无显著影响，对多巴胺代谢产物影响很小或无影响。间羟基类似物增加了已知会导致纹状体多巴胺持续减少的MPTP样化合物的种类，该化合物的位置异构体说明了这种作用对结构的严格依赖性。
