Human clinical studies, first report in 1967
L-DOPA treatment produced dramatic improvement in the symptoms of Parkinson’s patients.
This was the first discovery that a neurological disorder could be the result of a specific neurotransmitter disorder.
Review of Dopamine synaptic transmission
A. Synthesis of neurotransmitter: 1. Facilitated transport of precursor (amino acid tyrosine) into cell. 2. Conversion of precursor molecule into DA (produced by a series of enzyme-mediated chemical reaction). B. Package DA molecule into vesicles 1. Facilitated transport of DA into vesicle. C. Release (exocytosis) of DA into synapse 1. Action potential invades presynaptic terminal. 2. Opening of voltage-dependent Ca++ channels. 3. Influx of Ca++ into presynaptic terminal. 4. Ca++ mediated fusion of synaptic vesicle with presynaptic membrane. 5. DA exocytosis. D. Neurotransmitter action 1. DA binds to postsynaptic receptors; or 2. DA binds to presynaptic receptors E. Inactivation of DA 1. Re-uptake of DA into presynaptic neurons (transporter protein): a. recycling of DA into vesicles; or b. degradation of DA in neuron (monoamine oxidase-B) 7