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Sinemet and it's generic equivalents have carbidopa to inhibit peripheral conversion of l-dopa to dopamine. Two different rationales are stated as purposes. One is to prevent the conversion to dopamine because this causes nausea and tendency to vomit or feel like that is imminent. the second is to keep more of the l-dopa available in the bloodstream until it is absorbed by the brain. My query is in regard to the effects of carbidopa on the peripheral (parts of the body other than the brain) processes. Are some of the chronic sinemet effects due to the carbidopa? What about the need for dopamine by the dopaminergic neural cells in the gastro-intestinal tract. As I understand it, all the dopaminergic cells in the colon of Dr. Sidney Dorros were dead and contained Lewy bodies per the autopsy and special testing done by Dr. Ronald Pfeiffer. His death was deemed proximately due to lack of nerve cells sufficient to allow the normal function of de-fecating. Were data gathered on the carbidopa per se in the pre-approval testing of Lodosyn (which is carbidopa alone)? Are some of the long-term chronic medication effects different for the Madopar which uses a different chemical to inhibit the conversion enzyme? Has anyone tried switching from one to the other after eight or ten years? Were animal data on each of these drugs inclusive of long-term high dosages obtained? Were any of the effects correlated to the enhancement or retardation of gastrointestinal or other process decay of normal aging - or typical PD decay without carbidopa, etc. Another subject: Some references to lipofuscin (age darkening in the brain) have confused me. Is this only in dopaminergic neurons? Does it equate to neuromelanin? ... which is the blackening agent that makes the substantia nigra black? Or, is the substantia nigra black at birth? Are the skin age spots due to melanin? Is this melanin in nerve cells? I apologize for not knowing where to look for information about these curiosities I have had in my thoughts; I would appreciate answers or specific place(s) to look. Ron <[log in to unmask]> Ronald F. Vetter