The Clinical Syndrome of Striatal Dopamine Deficiency: Parkinsonism Induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)

Abstract

Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome that resembles Parkinson's disease. To compare the biochemical abnormalities produced by this compound in human beings with those occurring in Parkinson's disease, we examined biogenic amine metabolites in cerebrospinal fluid and urine from six patients with MPTP-induced parkinsonism and eight patients with Parkinson's disease. In both forms of parkinsonism, the cerebrospinal fluid levels of homovanillic acid, the major metabolite of dopamine, were reduced, whereas the levels of the serotonin metabolite 5-hydroxyindoleacetic acid were normal. The cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine in the brain, after adjustment for plasma MHPG, were elevated (greater than 6.0 ng per milliliter) in MPTP-induced parkinsonism, whereas MHPG levels were reduced (less than 6.0) in Parkinson's disease. Neurons containing norepinephrine in the brain are involved in the degenerative process of Parkinson's disease, whereas they are spared in MPTP-induced parkinsonism. The selective destruction by MPTP of nigrostriatal dopamine neurons that is responsible for the movement disorder also appears to result in an increase in central noradrenergic activity, which is not possible in Parkinson's disease. Thus, differences in central noradrenergic activity, reflected in cerebrospinal fluid levels of MHPG, distinguish these two forms of parkinsonism.