MPTP is a toxic substance that induces a Parkinsonism-like syndrome by destroying dopaminergic neurons in the CNS. A series of experiments demonstrated that MPTP per se is minimally toxic. Actually, it is a metabolite of MPTP, produced by MAO type B and called MPP+, that causes the neurological damage. Pretreatment by which of the following agents would minimize the damage induced by MPTP consumption?

Question

MPTP is a toxic substance that induces a Parkinsonism-like syndrome by destroying dopaminergic neurons in the CNS.  A series of experiments demonstrated that MPTP per se is minimally toxic.  Actually, it is a metabolite of MPTP, produced by MAO type B and called MPP+, that causes the neurological damage.  Pretreatment by which of the following agents would minimize the damage induced by MPTP consumption?

Quizplus · Accepted Answer

Selegiline is an inhibitor of MAO, type B. Since the actual causative agent of MPTP-associated Parkinsonism-type symptoms is formed by MAO, type B, pretreatment with selegiline can prevent this damage to dopaminergic neurons. Clinically, selegiline is used to delay the progression of Parkinson disease. (Choice A) Amantadine was designed as an antiviral influenza agent, but it is also known to have dopaminergic activity and possibly anticholinergic action as well; therefore, it may provide moderate improvement in patients with Parkinson disease. Amantadine and anticholinergic agents may produce undesirable side effects such as dry mouth, nausea, vomiting, blurring of vision, visual hallucinations, and other mental changes; they should be used with caution in the elderly. (Choice B) Dopamine is absent in the nigrostriatum of patients with Parkinson disease. Dopamine itself cannot be directly administered because it is unable to cross the blood-brain barrier. Levodopa, or L-dopa, is the immediate precursor of dopamine. It is taken up by the brain, engulfed in the striatum by cell processes that have cell bodies in the substantia nigra; then, in the substantia nigra, L-dopa is converted to dopamine, and released as a neurotransmitter. (Choice C) Levodopa is a dopamine analog that remains the most effective treatment for symptoms of Parkinson disease. Levodopa is absorbed in the small intestine via a large, neutral-amino-acid transporter system and is then converted to dopamine by the enzyme dopa-decarboxylase. Peripheral conversion to dopamine is largely responsible for the nausea and vomiting associated with L-dopa use. The addition of dopa-decarboxylase inhibitors (carbidopa) that do not cross the blood-brain barrier decrease the peripheral formation of dopamine, relieving the intense nausea and vomiting caused by levodopa alone. (Choice E) Pergolide is a dopamine agonist which directly stimulates dopamine D2 receptors. It provides only modest improvement in parkinsonian symptoms when used as monotherapy; however, this modest improvement may be sufficient to delay the introduction of levodopa by months or years, thus delaying levodopa-related side effects. Educational Objective: Many neurologists favor the use of combinations of selegiline, anticholinergics, and amantadine until they no longer provide control of symptoms. Only then is levodopa/carbidopa introduced.

MPTP Is a Toxic Substance That Induces a Parkinsonism-Like Syndrome