[Significance of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for the etiology and therapy of idiopathic Parkinson disease].
Exposure of drug addicts to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) has caused a Parkinsonian syndrome accompanied by a selective destruction of dopamine containing neurones in the pars compacta of the substantia nigra. MPTP in the human causes a severe irreversible state that very closely resembles idiopathic Parkinson's disease both in its clinical features and response to pharmacological treatment. Interest in potential environmental agents that might play a role in the aetiology of idiopathic Parkinson's disease is likely to increase as the result of the discovery of the relatively simple molecule MPTP which is highly toxic to the substantia nigra. Until the discovery of the neurotoxicity of MPTP there was no effective animal model of Parkinson's disease. Administration of PTP to monkeys induces persistent parkinsonism which responds to classical antiparkinsonian therapy. The morphological and biochemical changes in the brains of the animals are more limited and selective than those seen in idiopathic Parkinson's disease. The model of MPTP-treated monkeys appears to provide a useful testbed for the evaluation of future treatments for the disease. The precise mechanism of MPTP toxicity has yet to be determined and may provide the clue to the mechanism of neuronal death in Parkinson's disease. After entering the brain MPTP is oxidized to MPP+ (1-methyl-4-phenylpyridine) at an extraneuronal site.(ABSTRACT TRUNCATED AT 250 WORDS)
Lange
K W
KW
University Department of Neurology, Institute of Psychiatry, London.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D008125:Locus Coeruleus / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000188:drug therapy; D011725:Pyridines / Q000009:adverse effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*
D000978:Antiparkinson Agents; D011725:Pyridines; D011954:Receptors, Dopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Bedeutung des Neurotoxins MPTP für Atiologie und Therapie der idiopathischen Parkinsonkrankheit.