Synopses & Reviews
This volume provides a comprehensive reference on drugs employed to treat Parkinson's disease. Since pharmacology is dependent upon physiology, and physiology upon anatomy, the multiauthored contents build up from all these disciplines to applied therapeutics. Our knowledge of synaptic mechanisms in the striatum is reviewed; and drugs are considered as therapeutic tools to manipulate synaptic function. Methods of evaluating treatment in Parkinson's disease are discussed in order to provide a background against which the reader can determine whether therapeutic studies are meaningful. The volume deals with old drugs (anticholinergic agents), conventional drugs (levodopa and decarboxylase inhibitors) and new drugs (dopamine agonists). Drugs designed to modify the natural history of Parkinson's disease (antioxidants) are reviewed, and drugs employed to reduce adverse reactions are discussed (extracerebral D2 antagonists). Novel routes for administering drugs are included (parenteral infusions) and finally, current approaches to transplanting dopaminergic cells into the striatum are summarized. This book is intended to meet the needs of physicians who treat Parkinson's disease, to assist pharmacologists who are concerned with the development of improved methods for controlling symptoms, and to stimulate those neurobiologists who have an interest in attempting to slow down the inexorable progress of the disorder.
Synopsis
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.