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Drugs for the Treatment of Parkinson's Disease (Paperback, Softcover reprint of the original 1st ed. 1989)
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Drugs for the Treatment of Parkinson's Disease (Paperback, Softcover reprint of the original 1st ed. 1989)
Series: Handbook of Experimental Pharmacology, 88
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Over the last 25 years, few topics in medicine, and none in
neurology, sur- pass Parkinson's disease from the viewpOInt of
progress in understanding me- chanisms and treating symptoms. Our
entire concept of anatomy (the very ex- istence of a nigrostriatal
pathway) and physiology (dopaminergic trans- mission) has
undergrone a revolution as the result of studies on Parkinson's
disease leading to (a) the recognition of dopamine depletion as a
crucial bio- chemical feature, and (b) the ability to alleviate
symptoms by replenishing dopamine with levodopa. From this
background has emerged a subclassifica- tion of dopamine receptors
into Dl and D2 types, together with the develop- ment and
therapeutic application of synthetic molecules that function as
agonists at dopamine receptors. The pharmacological
interrelationship be- tween parkinsonism (inadequate dopamine) and
chorea (excessive dopamine) has been elucidated because
dopaminomimetic agents were found to alleviate parkinsonism and
induce chorea, while dopamine blocking drugs induced parkinsonism
and alleviated chorea. Pharmacokinetic manipulation of levo- dopa
achieved by adding extracerebral decarboxylase inhibitors
(carbidopa, benserazide) decreased certain side effects and
resulted in efficacy being at- tained with lower dosage.
Extracerebral dopamine receptor blockers have proved invaluable in
decreasing the emesis of dopaminomimetics, because the
dopaminoceptive chemoreceptor trigger zone is located outside the
blood- brain barrier. Recently, novel routes of administration of
antiparkinson drugs, such as subcutaneous infusion, have been
explored in an attempt to achieve more evenly sustained blood
concentrations of therapeutic agents.
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