SEROTONIN DOPAMINE

Serotonin dopamine balance: 5-HTP depletes dopamine

  Serotonin dopamine synthesis is caused by the enzyme "L-amino acid decarboxylase"  The implications of this fact are profound.

  Loading serotonin nutrients decreases dopamine synthesis. Loading dopamine nutrients decreases serotonin synthesis. From a clinical standpoint, what does this look like when the serotonin dopamine balance is ignored in this way?

  levodopa
 is used in the treatment of Parkinson's Disease. Long term use of levodopa
 without the use of properly balanced serotonin precursors causes serotonin depletion. A cause of this is levodopa
's competitive inhibition of 5-HTP synthesis.

  When serotonin depletion from levodopa
 is great enough the levodopa
 will not work and symptoms of disease return. With extreme depletion of serotonin the levodopa
 will not work at any dosing level and the effects both components of the serotonin dopamine system have quit.

  Administration of improperly balance 5-HTP, tryptophan, tyrosine or levodopa
 will decrease the synthesis. With administration of only one precursor the administered precursor dominates the synthesis enzyme compromising synthesis of the other system through competitive inhibition.

  The serotonin dopamine balance must be respected, urinary neurotransmitter testing when indicated is a key to this respect. In people suffering with Parkinsonism, the long-term administration of only levodopa
will result in levodopa
 not working, depression, and a host of other neurotransmitter depletion problems. Long term use of 5-HTP will deplete dopamine leading to dopamine depletion problems not the least of which is the 5-HTP quits working.

Serotonin Dopamine Metabolism

The Monoamine Oxidase (MAO) enzyme metabolize serotonin and the catecholamines (dopamine, norepinephrine, and epinephrine). The COMT metabolizes dopamine, norepinephrine, and epinephrine as well as illustrated to the left. The implications are profound.  The levels of these two enzyme systems are not static; they fluctuate in response to changing neurotransmitter levels.  When serotonin dopamine or norepinephrine levels are increased with administration of 5-HTP, tyrosine or levodopa, enzymatic activity also increases.

  Administration of levodopa
, tyrosine, tryptophan, and 5-HTP, increases MAO and COMT activity due to the increased dopamine or serotonin levels.  When improperly balanced levodopa
 is administered, both dopamine and serotonin will be subjected to increased metabolism as MAO enzyme increases in response to increased dopamine. Since serotonin has not experienced an increase in synthesis depletion occurs.  The same is true with 5-HTP administered without properly balanced dopamine precursors, metabolism depletes dopamine.  The bottom line is that the administration of unopposed precursors will deplete the other system as a result of the increased metabolism of MAO and COMT. The serotonin dopamine balance must be respected.

Serotonin Dopamine Uptake

  Synthesis required uptake of the precursors 5-HTP, tryptophan, tyrosine, or levodopa
.  Uptake occurs in numerous places throughout the body.  The organic cation transporter (OCT) found in the proximal convoluted renal tubule cells of the kidney are use as an uptake prototype (see illustration below).

  Neurotransmitters synthesized by the kidneys from dopa and 5-HTP are the source of serotonin dopamine norepinephrine and epinephrine found in the urine. Administration of significant levels of a single unbalanced precursor may overwhelm uptake. Competitive inhibition excludes uptake of other precursors. Administration of only 5-HTP competitively inhibits dopamine precursor uptake. Administration of only levodopa
 excludes serotonin precursor uptake. The serotonin dopamine balance must be respected.

  The illustration below represents a proximal tubule cell in the kidney. The serotonin dopamine or norepinephrine filtered by the glomerulous are metabolized by the MAO and COMT of the proximal tubule cell, very little makes it to the final urine.

   From a clinical standpoint, during long-term use levodopa
 becomes ineffective due to serotonin depletion. In order to prevent this 5-HTP needs to be administered with levodopa
 in proper balance. In medicine when the levodopa
 quits working the approach is to increase the levodopa
 dosing which depletes serotonin even more.

  When only 5-HTP is used in treatment, 5-HTP depletes dopamine, norepinephrine, and epinephrine levels. When dopamine levels drop low enough, 5-HTP becomes ineffective and the side effects of dopamine depletion occur. 5-HTP and dopa must be provided in proper balance to affect optimal serotonin dopamine balance. For years doctors have depleted serotonin levels in Parkinson's Disease patient by prescribing only levodopa
 with no properly balance serotonin precursors. People taking 5-HTP never realize that when the 5-HTP does not work or quits working it is because the serotonin dopamine system is not in balance.