ArticleCNS neuroscience & therapeutics2016
DopAmide: Novel, Water-Soluble, Slow-Release l-dihydroxyphenylalanine (l-DOPA) Precursor Moderates l-DOPA Conversion to Dopamine and Generates a Sustained Level of Dopamine at Dopaminergic Neurons.
Article in CNS neuroscience & therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 8 citations in OpenAlex.
- Novel anti-apoptotic L-DOPA precursors SuperDopa and SuperDopamide as potential neuroprotective agents for halting/delaying progression of Parkinson's disease.Cell death & disease · 2022Article
- Improving the Delivery of Levodopa in Parkinson's Disease: A Review of Approved and Emerging Therapies.CNS drugs · 2020Review
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1 author at 1 institution in 1 country.
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Abstract
backgroundLong-term l-dihydroxyphenylalanine (l-DOPA) treatment of Parkinson's disease (PD) is associated with motor complications known as l-DOPA-induced dyskinesias (LID) and on/off fluctuations, which are linked to unsteady pulsatile dopaminergic stimulation.
aimThe objective of this study was to improve l-DOPA treatment by slowing and stabilizing dopamine (DA) production in the brain and increasing water solubility to provide a rescue therapy for PD.
resultsWe synthesized l-DOPA-amide, a novel l-DOPA precursor called DopAmide. DopAmide is water soluble and, as a prodrug, requires hydrolysis prior to decarboxylation by the aromatic l-amino acid decarboxylase (EC 4.1.1.28; AAAD). In the 6-OH-dopamine (6-OHDA)-lesioned rats, DopAmide maintained steady rotations for up to 4 h compared with 2 h by l-DOPA, suggesting that this rate-limiting step generated a sustained level of DA at dopaminergic neurons. Pharmacokinetic studies showed elimination half-life of l-DOPA in the plasma after DopAmide treatment of t1/2 = 4.1 h, significantly longer than t1/2 = 2.9 h after treatment with l-DOPA, consistent with the 6-OHDA results.
conclusionsThe slow conversion of DopAmide to l-DOPA provides a sustained level of DA in the dopaminergic cells, shown by the long 6-OHDA steady rotations. The water solubility and improved bioavailability may help reduce medication frequency associated with l-DOPA treatment of PD. Sustained levels of DA might lower the super-sensitization of DA signaling and potentially attenuate l-DOPA adverse effects.
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