Advances in the neuropharmacology of Parkinsonism

Advances through basic research have elucidated the disturbances of neurotransmitter function in Parkinson's disease, with findings directly applicable to drug therapy. Dopamine has replaced acetylcholine and norepinephrine as the most studied neurotransmitter, with both conceptual and practical developments, exemplified by the hypothesis of cyclic adenosine monophosphate as a 'second messenger', and new therapeutic agents. We now have rationally designed in vitro and in vivo tests for the evaluation of dopaminergic compounds instead of entirely empiric screening procedures. We are starting to identify different categories of dopaminergic receptors and to manipulate them selectively, with gains in understanding the physiologic input to the striatum. Crucial questions remain, including how dopamine modulates striatal output and what causes the parkinsonian degeneration of the nigrostriatal pathway. Developing knowledge on synaptic physiology and pharmacology may lead to better therapy.