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Chapter-10 Antiparkinsonian Drugs

BOOK TITLE: Drug Screening Methods

Author
1. Mathur Rajani
ISBN
9788180613975
DOI
10.5005/jp/books/10243_10
Edition
1/e
Publishing Year
2004
Pages
13
Author Affiliations
1. Delhi Institute of Pharmaceutical Sciences and Research (Delhi University), Pushp Vihar, New Delhi, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), MB Road, Pushp Vihar, Sector-3, New Delhi (India), All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India, Delhi Institute of Pharmaceutical, Sciences and Research, Pushp Vihar, Sector-3, New Delhi, India, Delhi Institute of Pharmaceutical, Sciences and Research, Pushp Vihar Sector-3, New Delhi, India, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), University of Delhi, New Delhi, India, Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi, Pushp Vihar, Sector-3, New Delhi, India, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India
Chapter keywords
Parkinson’s disease (PD), progressive neurodegenerative disorder, dopaminergic neurons, substantia nigra, rat striatal slices, striatum, brain region, Parkinsonism, neurotransmitters, dopamine, acetylcholine, dopamine-stimulated adeny, lyl cyclase activity, radioligand binding studies, dopamine receptors, dopamine release, synaptosomes, behavioral models of Parkinsonism, reserpine-induced Parkinsonism, assessment of hypokinesia, assessment of muscular rigidity, assessment of catatonia, neuroleptics-induced Parkinsonism, neuroleptics

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by selective and extensive loss of dopaminergic neurons of substantia nigra. In vitro and ex vivo models are described. Experiments using rat striatal slices are discussed. Striatum is the brain region, which is primarily affected in Parkinsonism. The release of neurotransmitters, such as dopamine and acetylcholine in response to test agent serves as a good in vivo marker of its activity. Dopamine-stimulated adenylyl cyclase activity is discussed. Radioligand binding studies for D1 and D2 dopamine receptors and dopamine release from synaptosomes are explained. Behavioral models of Parkinsonism are described. Reserpine-induced Parkinsonism is explained. Assessment of hypokinesia and assessment of muscular rigidity are discussed. Assessment of catatonia is discussed. Neuroleptics-induced Parkinsonism is explained. Neuroleptics act by blocking striatal dopamine receptors and are useful for the management of psychosis in patients. Cholinomimetics-induced Parkinsonism is discussed. In PD loss of nigrostriatal dopaminergic inhibitory neurons results in cholinergic hyperactivity. Surgical induction is explained. Unilateral administration 6–OH-DA in the substantia nigra, ventral tegmentum or medial forebrain bundle in rats produces degeneration of the nigrostriatal pathway. Bilateral administration of 6-OH-DA in the medial forebrain bundle at the level of the lateral hypothalamic area results in a widespread depletion of regional brain catecholamine content and is accompanied with severe neurobehavioral disturbances. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is an environmental toxin, which produces a parkinsonian syndrome after its conversion to 1-methyl-4-phenylpyridine (MPP+) by B-form monoamine oxidase (MAO) in the brain. Monitoring dopamine concentration using microdialysis is discussed. Microdialysis has become a widely used method for the analysis of the extracellular fluid composition in anaesthetized and moving animals. Effect of dopamine receptor stimulation on electrophysiological output from rat basal ganglia is described.

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