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For Ron Vetter, copy to Ron Reiner Hello all, and hello Ron Vetter. Thanks for the long email, which I will try=20 to answer. First: How do I know what happens to a normal person taking a large dose of=20 Sinemet :- Because my friendly neuroologist at Nottingham U told me so. He did not gove me a bunch of references, but I have a high regard for his knowledge, and if he says it is so, that's good enough for me. (To expand=20 on 'virtually nothing' : What he actually said was "They might get a slight=20 headache, but apart from that, nothing happens." Second: I am quite sure that there is no difference between normal people and PWPS all the way from the stomach to the brain side of the blood-brain=20 barrier. Thus the hypothetical 'large tablet' that I refer to must arrive in the brain, in=A0exactly the same quantity and format in either case. This is a fundamental point about PD - we are just like everyone else, apart from our inability to produce Dopamine. Third: Your description of the dopamine being held in containers at the=20 synapses - available to be released to cross the nerve-to-nerve gap is not quite right: I refer you to pages 26 to 30 of 'The Parkinson's Handbook' (McGoon) and especially p.28. The 'message' that is so important to us is an electrical charge, not a chemical one. The charge can only cross the gap from one axon to the next if the conductive properties of the fluid bathing=20 the axon are favourable, and this depends on the quantity and quality of the Dopamine which the axon receives. So the nerve cells in the Substantia Nigra manufacture Dopamine, which=20 travels down the axon to the next nerve cell, where it bathes the synapse. The Dopamine is not the message, and the time at which this process occurs is not necessarily related to the timing of the action represented by the=20 electrical impulse. All that matters is that when the electrical charge=20 passes from the brain to the muscle, the axons which it encounters must=20 previously have been bathed by the appropriate neurotransmitter. What follows is my personal speculation, so don't blame Dr McGoon: It occurs=20 to me that as the electrical charge zips down the axons, encountering synapses along the way ( like points in a railroad track), it may be just as important that certain synapses are 'dry' and do not propagate the signal any further. This may be how dyskinesias occur: through excess levodopa bathing the wrong synapses. Don't forget that in my vision of the whole thing, an excess of=20 Dopamine cannot exist in a normal brain. -- =20 Brian Collins <[log in to unmask]>