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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.
Sommario
1 Neurophysiology of Basal Ganglia.- 2 Pathology of Parkinson's Syndrome.- 3 Biochemical Neuroanatomy of the Basal Ganglia.- 4 Receptors in the Basal Ganglia.- 5 Imaging the Basal Ganglia.- 6 The Neurochemical Basis of the Pharmacology of Parkinson's Disease.- 7 Pyridine Toxins.- 8 The Relationship Between Parkinson's Disease and Other Movement Disorders.- 9 Evaluation of Parkinson's Disease.- 10 Clinical Trials for Parkinson's Disease.- 11 Experimental Therapeutics Directed at the Pathogenesis of Parkinson's Disease.- 12 Anticholinergic Drugs and Amantadine in the Treatment of Parkinson's Disease.- 13 The Pharmacology of Levodopa in Treatment of Parkinson's Disease: An Update.- 14 Adverse Effects of Levodopa in Parkinson's Disease.- 15 Monoamine Oxidase Inhibitors in Parkinson's Disease.- 16 Clinical Actions of l-Deprenyl in Parkinson's Disease.- 17 Update on Bromocriptine in Parkinson's Disease.- 18 Pergolide in the Treatment of Parkinson's Disease.- 19 Lisuride Pharmacology and Treatment of Parkinson's Disease.- 20 Domperidone and Parkinson's Disease.- 21 New Routes of Administration for Antiparkinsonian Therapy.- 22 Treatment of Parkinsonian Features in Neurological Disorders Other than Parkinson's Disease.- 23 Management of Psychiatric Symptoms in Parkinson's Disease.- 24 Intracranial grafts for the treatment of Parkinson's Disease.
