Developments in the pharmacology and therapeutics of parkinsonism.

Abstract

AbstractAdvances in synaptic pharmacology have led to new approaches to understanding and attempting to alleviate the disturbances in neurotransmission that occur in parkinsonism. Techniques which were initially developed to elucidate normal synaptic phenomena are being employed to screen potential therapeutic agents for efficacy, relative potency, and neurotoxicity and to analyze the mechanism of action of antiparkinsonian drugs. In vitro methods utilizing striatal tissue include the assay of dopamine release, the determination of active dopamine reuptake, the displacement of ligands from dopamine receptors, and the stimulation of dopamine‐sensitive adenylate cyclase. In vivo test systems in rats comprise alleviation of the reserpine syndrome, induction of stereotypic behavior, measurement of turning after unilateral nigrostriatal lesions, evaluation of regional changes in the concentration of dopamine and its metabolites, and recording of single‐unit responses in the brain. With these tools, it is proving possible to sustain progress in the search for improved treatment, exemplified by current experimental studies with dopaminergic agonists and selective inhibitors of monoamine oxidase isoenzymes. The pursuit of practical applications has been accompanied by conceptual advances, such as the proposal that cyclic nucleotides are “second messengers” in the nigrostriatal pathway and the recognition of certain amino acids and peptides as synaptic transmitters or modulators in the basal ganglia.