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Impairment of Serotonergic Transmission by L-DOPA - Mechanisms and Implications

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Old 09-13-2017, 06:15 AM   #1
jeffreyn
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Default Impairment of Serotonergic Transmission by L-DOPA - Mechanisms and Implications

"The interaction between L-DOPA and 5-HT transmission is especially relevant in those Parkinson's disease (PD) patients that suffer dyskinesia, comorbid anxiety or depression, since the efficacy of antidepressants or 5-HT compounds may be affected."

Frontiers | Impairment of Serotonergic Transmission by the Antiparkinsonian Drug L-DOPA: Mechanisms and Clinical Implications | Frontiers in Cellular Neuroscience
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Old 09-13-2017, 07:16 AM   #2
billbobby21
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Quote:
Originally Posted by jeffreyn View Post
"The interaction between L-DOPA and 5-HT transmission is especially relevant in those Parkinson's disease (PD) patients that suffer dyskinesia, comorbid anxiety or depression, since the efficacy of antidepressants or 5-HT compounds may be affected."

Frontiers | Impairment of Serotonergic Transmission by the Antiparkinsonian Drug L-DOPA: Mechanisms and Clinical Implications | Frontiers in Cellular Neuroscience
This is why Dr. Marty Hinz's methodology of treatment prescribes the use of 5-htp for control of Serotonin depletion through competitive inhibition at the AADC enzyme by 5-htp and L-dopa. With increasing L-dopa administration, you get less enzyme activity by 5-htp, reducing the amount of Serotonin being produced leading to less being available in the pre-synaptic vesicles and then ultimately in the synaptic cleft when post synaptic activation is required. 5-htp use in the treatment of Parkinsons disease can also control nausea, which is the main dosage limiter as patients will experience intolerable nausea once the L-dopa gets high enough which will create a dosage barrier than cannot be overcome until it is resolved. The current resolution for this issue presently is Carbidopa, but it comes with a myriad of side effects. If 5-htp is able to resolve nausea just as well, if not better, as well as preventing Serotonin depletion, leading to resolution of L-dopa side effects like depression, then it is clearly the superior option. Carbidopa also decreases the effectiveness of L-dopa as it depletes Vitamin B6 which is a co-factor in the conversion of L-dopa to Dopamine.
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Old 09-15-2017, 12:04 AM   #3
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Thanks for your input billbobby21.

When you say "Carbidopa also decreases the effectiveness of L-dopa as it depletes Vitamin B6 which is a co-factor in the conversion of L-dopa to Dopamine.", you seem to be focusing on the tree and ignoring the forest.

Carbidopa can not cross the blood brain barrier (BBB). Thus, carbidopa only inhibits the enzymatic action of AADC outside of the brain, which actually INCREASES the effectiveness of L-dopa, enabling much smaller doses of L-dopa to be used. When carbidopa is not used (e.g. Hinz protocol) much larger doses of L-dopa are needed, and these large doses of L-dopa can cause nausea (unless compensated for by the use of (large doses of?) 5-HTP (and other supplements?).

The main message I get from the research paper is that the effect of L-dopa on the serotonergic system (in different parts of the brain) is quite complex, and still not fully understood.

I also noticed that this research paper makes no reference to the research papers written by Hinz et al.

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Old 09-17-2017, 05:44 AM   #4
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Thanks jeffreyn.

I think that the review is very informative - a good balance between the basic science and its potential (and important) clinical implications.
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Old 09-18-2017, 07:26 AM   #5
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By co-incidence, Prof. Frank Church has recently written an interesting post about B vitamins (folate, B6, B12) and carbidopa/levodopa therapy.

The main message seems to be that, if you take c/l, don't overdo the vitamin B6 supplements.

B Vitamins (Folate, B6, B12) Reduce Homocysteine Levels Produced by Carbidopa/Levodopa Therapy | Journey with Parkinson's
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