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MPTP: A Parkinsonism-causing Neurotoxic Substance

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Current Aspects of the Neurosciences

Abstract

The past six years have witnessed an intense research effort centred around MPTP, l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. This research was triggered by the appearance in 1983 of a paper by Langston et al. implicating MPTP as a causative agent in a Parkinson’s disease-like condition found among drug abusers in northern California who had self-administered a street drug sold as a ‘synthetic heroin’. Langston et al. (1983) initially described four affected individuals who had developed severe parkinsonism soon after intravenous self-administration of a few doses of the street drug preparation. The preparation was intended to contain l-methyl-4-phenyl-4-propionoxypiperidine (MPPP), a compound resembling meperidine chemically and pharmacologically (Figure 1). The intended compound can be classed as a ‘designer drug’, an agent with pharmacological activity (in this case, narcotic activity) like that of an abused drug but chemically distinct from drugs that are controlled substances. MPTP was a by-product of the synthesis; it has no narcotic activity. The difference in structure between MPPP and meperidine is slight, and their pharmacological effects are similar. However, esterolysis of MPPP produces a compound that can undergo dehydration to form MPTP. Meperidine itself has a carbon-carbon bond off the piperidine ring instead of the carbon-oxygen bond in MPPP, so meperidine would not form the degradation product MPTP.

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  1. Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA

    Ray W. Fuller

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  1. Nuffield Laboratory of Ophthalmology, University of Oxford, 0X26AW, Oxford, UK

    Neville N. Osborne

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Fuller, R.W. (1990). MPTP: A Parkinsonism-causing Neurotoxic Substance. In: Osborne, N.N. (eds) Current Aspects of the Neurosciences. Palgrave, London. https://doi.org/10.1007/978-1-349-10997-5_6

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  • DOI: https://doi.org/10.1007/978-1-349-10997-5_6

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