Drug induced parkinsonism: reserpine, haloperidol, metoclopramide, MPTP

1. Drug induced parkinsonism
Domina Petric, MD

2. 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.

3. 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.

4. 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.

5. 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.

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