Dopaminergic receptor agents and the basal ganglia: pharmacological properties and interactions with the GABA-ergic system.

Abstract

In the present series of studies, attention was focussed particularly on dopaminergic D2 receptor compounds, with emphasis on the enantiomers of the potent and selective dopamine D2 receptor agonist N-0437. Drugs that display activity at D2 receptors are of great interest as potentially new therapeutic agents for the treatments of Parkinson’s disease and schizophrenia. With these therapeutic uses in mind, the pharmacological profiles of the enantiomers of N-0437 were considered. The pathophysiology of Parkinson’s disease, and to a lesser extent of schizophrenia, is thought to be related to disturbances in the functioning of the basal ganglia. Therefore, in order to understand the neuropathology of these diseases, it is essential to gain further insight into the normal functioning of the basal ganglia. Hence, experiments in this thesis were also directed to further clarification of neuronal interactions in the basal ganglia. In summary, the aims were (1) to characterize the pharmacological properties of the enantiomers of the D2 agonist N-0437; (2) to assess their potential as therapeutic agents in the treatment of Parkinson’s disease and schizophrenia; (3) to study dopamine-GABA interactions in the basal ganglia.