The master neurotransmitters (serotonin, dopamine, norepinephrine, and epinephrine) do not cross the blood brain barrier. The only way to increase central nervous system levels of these neurotransmitters is by providing amino acid precursors that cross the blood brain barrier and synthesized by specific areas of the brain into neurotransmitters.

  There are many clinical observations that verify the fact that these neurotransmitters do not cross the blood brain barrier. For example, a Parkinson patient presents in the emergency room with shock and a dopamine drip is started. No relief of the Parkinson symptoms is seen since dopamine does not cross the blood brain barrier.

METABOLISM COMPETITION

The Monoamine Oxidase (MAO) and Catecholamine-O-Methyl Transferase (COMT) enzymes metabolize serotonin and the catecholamines, 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 neurotransmitter levels are increased, enzymatic activity also increases.

            If you administer L-dopa or 5-HTP, the activity of MAO and COMT increases due to the increase in dopamine or serotonin levels respectively.  The problem occurs when L-dopa is administered without 5-HTP, both dopamine and serotonin will be subjected to increases in metabolism by these two enzyme systems.  However, serotonin will not experience an increase in production, which leads to further depletion.  The same rule is true of 5-HTP administered without the use of dopamine precursors.  The bottom line is that the administration of unopposed 5-HTP or L-dopa will deplete the other system as a result of the increased metabolism of MAO and COMT.

  In order for the synthesis of monoamine neurotransmitters to occur, the amino acid precursors must undergo uptake into the cells performing synthesis.  This process occurs in numerous places throughout the body, as listed in table 1 to the right.  The “cation uptake ports” found in the proximal convoluted renal tubule cells are a prototype for amino acid uptake, the illustration below at the top center.

  Neurotransmitters synthesized by the kidneys are the source of urinary serotonin and catecholamines.  Serotonin and the catecholamines are synthesized by the kidneys, then excreted into the urine or secreted into the system.  Uptake is affected by administration of a single amino acid precursor or improperly balanced amino acid precursors as may overwhelm and compete with uptake of the other amino acids. Administration of only L-dopa inhibits uptake of 5-HTP. Administration of only 5-HTP has the same effect on L-dopa uptake. 

  In subjects who are depressed or suffering from disease where neurotransmitter levels are not high enough, synaptic neurotransmitter levels are below the levels needed to prevent disease symptoms.

  Serotonin reuptake inhibitors, dopamine reuptake inhibitors, norepinephrine reuptake inhibitors, amphetamines, and cocaine block the reuptake of neurotransmitters. This leads to a decrease in presynaptic neurotransmitter levels (where neurotransmitters are safe from enzymatic breakdown). The blocking of neurotransmitter reuptake increases the number of neurotransmitters in the synapse and increases the probability that neurotransmitters will experience enzymatic metabolism.  

  Overtime, the net effect of enzymatic metabolism is the depletion of neurotransmitter levels in the central nervous system. Neurotransmitters do not cross the blood brain barrier. Therefore, the only way to increase central nervous system levels or to prevent the overall depletion of neurotransmitters is to provide amino acid precursors, which cross the blood brain barrier and are able to be synthesized into neurotransmitters.