Rose S, Nomoto M, Jackson E A, Gibb W R, Jenner P, Marsden C D
Parkinson's Disease Society Experimental Research Laboratories, Biomedical Sciences Division, King's College, London, U.K.
Eur J Pharmacol. 1990 May 31;181(1-2):97-103. doi: 10.1016/0014-2999(90)90249-6.
Four adult marmosets were treated with increasing doses of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) in the range 0.23-4.3 mg/kg i.p. to give a cumulative dose of 11.0-11.6 mg/kg over a 6-10 day period. After 4 days of treatment, and as the dosage was gradually increased, the animals exhibited mild motor deficits. These abnormalities slowly declined over the following 1-6 week period. In contrast, similar treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1-4 mg/kg i.p.) for 3-5 days in a cumulative dose of 6.9-9.2 mg/kg produced gross impairment of motor function which persisted throughout the 5 weeks period of observation. Administration of 2'-methyl-MPTP for 6-10 days caused some decrease in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), but not homovanillic acid (HVA) content in the caudate nucleus in animals 5-6 weeks after the start of treatment. There was a small decrease in [3H]dopamine uptake into putamen synaptosomes. This contrasted with the marked decreases in all these parameters observed after MPTP treatment of common marmosets. Histological examination of the substantia nigra from the four animals treated with 2'-methyl-MPTP did not show degeneration or loss of dopamine-containing cell bodies in the zona compacta. In contrast, MPTP caused severe destruction of these pigmented nigral neurones. In the common marmoset 2'-methyl-MPTP does not appear to show the same neurotoxic action as MPTP itself. This contrasts with findings in the mouse where 2'-methyl-MPTP is more toxic to dopamine-containing cells of substantia nigra than MPTP.
给4只成年狨猴腹腔注射剂量递增的1-甲基-4-(2'-甲基苯基)-1,2,3,6-四氢吡啶(2'-甲基-MPTP)，剂量范围为0.23-4.3mg/kg，在6-10天内累积剂量达到11.0-11.6mg/kg。治疗4天后，随着剂量逐渐增加，动物出现轻度运动功能障碍。这些异常在接下来的1-6周内逐渐减轻。相比之下，用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)(1-4mg/kg腹腔注射)对普通狨猴进行类似治疗3-5天，累积剂量为6.9-9.2mg/kg，会导致运动功能严重受损，且在整个5周的观察期内持续存在。在治疗开始5-6周后，给动物连续6-10天注射2'-甲基-MPTP会使尾状核中的多巴胺和3,4-二羟基苯乙酸(DOPAC)含量有所下降，但高香草酸(HVA)含量未下降。壳核突触体对[3H]多巴胺的摄取略有减少。这与用MPTP治疗普通狨猴后观察到的所有这些参数的显著下降形成对比。对接受2'-甲基-MPTP治疗的4只动物的黑质进行组织学检查，未发现致密带中含多巴胺细胞体的变性或丢失。相比之下，MPTP会导致这些色素性黑质神经元严重破坏。在普通狨猴中，2'-甲基-MPTP似乎没有表现出与MPTP本身相同的神经毒性作用。这与在小鼠中的发现形成对比，在小鼠中2'-甲基-MPTP对黑质中含多巴胺细胞的毒性比MPTP更大。
