Drug induced parkinsonism Domina Petric, MD

Drug induced parkinsonism Reserpine and the related drug tetrabenazine deplete biogenic monoamines from their storage sites. Haloperidol, metoclopramide and the phenothiazines block dopamine receptors. These drugs may produce a parkinsonian syndrome, usually within 3 months after introduction.

Drug induced parkinsonism The disorder tends to be symmetric with inconspicuous tremor. The syndrome is related to high dosage and clears over several weeks or months after withdrawal. If treatment is necessary, antimuscarinic agents are preferred. Levodopa is of no help if neuroleptic drugs are continued and may aggravate the mental disorder.

MPTP and parkinsonism MPTP is a protoxin that is converted by monoamine oxidase B to N-methyl-4-phenylpyridinum (MPP+). MPP+ is selectively taken up by cells in the substantia nigra through an active mechanism normally responsible for dopamine reuptake. MPP+ inhibits mitochondrial complex I: inhibits oxidative phosphorylation.

MPTP and parkinsonism The interaction of MPP+ with complex I probably leads to cell death and thus to striatal dopamine depletion and parkinsonism. In 1983, MPTP-parkinsonism was discovered in individuals who attempted to synthesize and use a narcotic drug related to meperidine, but actually synthesized and self-administered MPTP.

Katzung, Masters, Trevor. Basic and clinical pharmacology. Literature Katzung, Masters, Trevor. Basic and clinical pharmacology.