http://amec.glp.net/c/document_libra...DLFE-20239.pdf

i remembered reading that sinemet CR half life is enhanced by food, was researching this and saw this article again, great discussion of the major L-DOPA , L-DOPA VS DOPAMINE AGONIST clinical trials.

i found this observation interesting, might be a little hard to read, had to reassemble it after cutting from pdf:

In the early 1990s, a number of in vitro studies demonstrated that high doses of LD can be toxic to dopaminergic neurons in cell culture, 30–32 causing some PD specialists to recommend withholding LD for as long as possible. 33 Since that time, data have accumulated showing that LD may also have protective effects for cultured dopamine neurons, depending on experimental conditions, such as presence or absence of glia 34,35 or ascorbic acid, 36,37 as well as LD dose used. 38 In addition, many in vivo
studies could not find evidence of LD-induced neurodegeneration in normal rodents, 39 primates, 40 and nonparkinsonian humans,
41 and some have even reported neuroprotective effects of LD on midbrain dopaminergic neurons. 42,43 Of particular interest are pathology reports from patients with essential tremor or dopa-responsive dystonia who had been chronically exposed to large amounts of LD over many years. None of these patients have shown evidence of substantia nigra degeneration at autopsy.

Thanks ST, this was a great review, particularly for early stagers like me.

your're welcome.

kind of posted that for the newly diagnosed who can't tolerate agonists or aren't getting adequate symptom relief won't be so scared to try l-dopa.

for someone like me, whose insurance won't pay anything for neupro or name brand requip xl and is just taking a combo of sinemet and sinemet-cr because can't tolerate mirapex or requip, it certainly isn't a "honeymoon" anymore after 12 years because of the short sinemet half and sudden wearing off. and having to be sure i don't eat too much protein within an hr of a dose, a cup of cooked lentils will negate a dose. so at least for me sinemet kind of controls my life much more than a long lasting agonist would. hoping the nasal l-dopa if it gets approved and i can afford it will smooth out the doseages and make treating sudden wearing off a few minute fix. might just be pie in the sky.

that's why agonists were developed, long half life and i assume no protein interference.

Really interesting. The link no longer works. The new link of "Levodopa in the treatment of Parkinson’s disease: an old drug still going strong" is Europe PMC