5-HTP, 5HTP, serotonin, dopamine, L-dopa neurotransmitter, tyrosine

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REUPTAKE INHIBITOR DRUGS:

This is a partial list.

Prozac

Zoloft

Luvox

Celexa

Lexapro

Effexor

Wellbutrin

Cymbalta

Paxil

Meridia

Amitriptyline

Nortriptyline

Serzone

Norpramin

Pristiq

Strattera

Asendin

Ludiomil

Zyban

Elavil

Sinequan

Phentermine

Tenuate

Bontril

Amphetamines

5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels

L-dopa aka dopa depletes serotonin neurotransmitter levels

tyrosine aka L-tyrosine depletes serotonin neurotransmitter levels

Reuptake inhibitor depression and ADHD drugs deplete serotonin and/or dopamine neurotransmitter levels

5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels

L-dopa aka dopa depletes serotonin neurotransmitter levels

tyrosine aka L-tyrosine depletes serotonin neurotransmitter levels

Reuptake inhibitor depression and ADHD drugs deplete serotonin and/or dopamine neurotransmitter levels

5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels

tyrosine aka L-tyrosine depletes serotonin neurotransmitter levels

Reuptake inhibitor depression and ADHD drugs deplete serotonin and/or dopamine neurotransmitter levels

5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels

Coast of Maine photo by Marty Hinz, MD

The neurotransmitter approach used in over 900 medical clinics

This web page discusses how serotonin and dopamine reuptake inhibitors used to treat depression, ADHD, etc. as well as 5-HTP, L-dopa, and tyrosine deplete neurotransmitters. Comprehensive management of the problem of serotonin and dopamine depletion is discussed on other pages of this web site.

NEUROTRANSMITTER DEPLETION

BY DEPRESSION AND ADHD DRUGS,

5-HTP, L-DOPA AND TYROSINE

By: Marty Hinz, MD

President Clinical Research

NeuroResearch Clinics, Inc

Common thinking in medicine is that low serotonin and dopamine neurotransmitter levels cause disease such as depression, ADHD, anxiety, panic attacks, insomnia and a host of other diseases. In review of tens of thousands of serotonin and dopamine neurotransmitter labs performed by DBS Labs it is apparent that this thinking is flawed. All patients, with and without disease such as depression, ADHD, etc., have the same serotonin and dopamine neurotransmitter levels prior starting 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa treatment. The problem is not low levels of serotonin and dopamine neurotransmitter levels causing disease such as depression, ADHD, etc. it is levels that are not high enough serotonin and dopamine neurotransmitter levels to compensate for serotonin and dopamine "bundle damage" in the brain. Either way there is not high enough serotonin or dopamine neurotransmitter levels to allow the patient to be free of depression and ADHD symptoms. 5-HTP aka 5HTP or 5 HTP

In treating disease such as depression, ADHD, etc. one of the basic foundations doctors work from is, "First do not harm". In other words, "don't make the patient or the patient's disease worse". If the doctor treats a patient and makes the cause of the problem worse the doctor has just violated this basic foundation of medicine. Depression and ADHD drugs as well as 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa all deplete serotonin and dopamine neurotransmitter levels if not used properly. Herein lies the problem, the standard approach in medicine to using depression and ADHD drugs, 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa is not proper and facilitates depletion of serotonin and dopamine neurotransmitter levels when increased levels are needed for relief of symptoms. L-dopa aka dopa

When using 5-HTP aka 5HTP or 5 HTP alone, only 10% to 15% of patients report relief of symptoms. 20% to 25% report some improvement. In fact treatment with 5-HTP aka 5HTP or 5 HTP has about the same effectiveness as reported in depression and ADHD studies for a sugar pill (placebo). Of concern here is the fact that 5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels. When dopamine depletion is enough any effects seen with 5-HTP aka 5HTP or 5 HTP quit and symptoms of disease such as depression, ADHD, etc. return. The patient is then left in a state where the serotonin and dopamine neurotransmitter molecules are worse off than at the start of treatment.

L-dopa aka dopa and tyrosine aka L-tyrosine are synthesized by the brain into dopamine. L-dopa is used to treat Parkinson's disease in the form of the drug Sinemet. L-dopa aka dopa depletes serotonin neurotransmitter molecules. When enough serotonin is depleted the L-dopa aka dopa quits working and symptoms of disease, Parkinsonism, depression, ADHD, etc. return. neurotransmitter

Serotonin and dopamine reuptake inhibitor drugs used to treat depression and ADHD deplete serotonin and dopamine. The only way to raise serotonin and dopamine neurotransmitter levels in the brain is to give the body properly balanced 5-HTP aka 5HTP or 5 HTP (5HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa nutrients. There is no other way to truly increase serotonin and dopamine neurotransmitter levels in the brain, none. Serotonin and dopamine neurotransmitter levels the brain is just the tip of the iceberg. Serotonin and dopamine neurotransmitter molecules regulate and control virtually every function in the body.

The serotonin and dopamine reuptake inhibitor depression and ADHD drugs used to treat depression and ADHD do nothing to increase serotonin and dopamine neurotransmitter levels in the brain they work by moving serotonin and dopamine neurotransmitter molecules from one place to another in the brain. In the process the reuptake inhibitor depression and ADHD drugs deplete serotonin and dopamine neurotransmitter levels and making clinical symptoms of depression, ADHD, etc. worse including an increased risk of suicide.

From The

"Zoloft Prescribing Information"

For Physicians

Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.

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EFFECTIVENESS

An in-depth discussion on the effectiveness of reuptake inhibitor depression and ADHD drugs.

DEPLETION

An in-depth discussion on how reuptake inhibitor depression and ADHD drugs deplete the neurotransmitter levels of serotonin, dopamine and norepinephrine.

HABIT FORMING

An in-depth discussion on why reuptake inhibitor depression and ADHD drugs are habit forming

Medicines currently used in medicine that deplete serotonin and dopamine with how to prevent depletion.

SUBSTANCE: 5-HTP aka 5HTP or 5 HTP depletes dopamine

PREVENT DEPLETION:

5-HTP aka 5HTP or 5 HTP needs to be given with properly balanced tyrosine aka L-tyrosine and/or L-dopa aka dopa to prevent depletion of dopamine by 5-HTP aka 5HTP or 5 HTP.

SUBSTANCE: L-dopa aka dopa depletes serotonin

PREVENT DEPLETION:

L-dopa aka dopa need to be given with properly balanced 5-HTP aka 5HTP or 5 HTP to prevent depletion of serotonin by L-dopa aka dopa.

SUBSTANCE:

Reuptake inhibitor depression and ADHD drugs deplete serotonin and/or dopamine and/or norepinephrine

PREVENT DEPLETION:

5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa need to be given in proper balance anytime one of these reuptake inhibitor depression or ADHD drugs is taken to prevent depletion of serotonin, dopamine and norepinephrine by the depression or ADHD drugs.

REUPTAKE INHIBITOR DEPRESSION AND ADHD DRUGS:

This is a partial list.

Prozac

Zoloft

Luvox

Celexa

Lexapro

Effexor

Wellbutrin

Cymbalta

Paxil

Meridia

Amitriptyline

Nortriptyline

Serzone

Norpramin

Pristiq

Strattera

Asendin

Ludiomil

Zyban

Elavil

Sinequan

Phentermine

Tenuate

Bontril

Amphetamines

Cocaine

Ecstasy

bdt

THE BUNDLE DAMAGE THEORY

The bundle damage theory states:

Serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter dysfunction disease symptoms, such as symptoms of depression and ADHD, develop when the electrical flow through the neuron bundles that regulate function is compromised by damage to the individual serotonin and dopamine neurons or the neuron components composing the serotonin and dopamine neuron bundles which conducts electricity to regulate or control function. In order to optimally restore serotonin and dopamine neuron bundle regulatory function, synaptic serotonin and dopamine neurotransmitter levels of the remaining viable serotonin and dopamine neurons must be increased to levels higher than is normally found in the system, which restores adequate electrical outflow resulting in relief of symptoms and optimal regulatory function.

first

neurotransmitter serotonin dopamine 5-HTP L-dopa tyrosine symbol

FIRST - DO NO HARM

Ø Administering only 5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels.

Ø Administering only L-dopa aka dopa or tyrosine aka L-tyrosine depletes serotonin neurotransmitter levels.

Ø Improperly balanced 5-HTP aka 5HTP or 5 HTP, L-dopa aka dopa, and tyrosine aka L-tyrosine cause depletion of serotonin and dopamine neurotransmitter levels.

Ø When serotonin depletion is great enough from improperly balanced 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa, the clinical effects from L-dopa aka dopa are no longer seen, i.e. the L-dopa aka dopa quits working when you deplete the serotonin neurotransmitter molecules.

Ø When dopamine depletion from improperly balanced 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa is great enough, the clinical effects from 5-HTP aka 5HTP or 5 HTP are no longer seen, i.e. the 5-HTP aka 5HTP or 5 HTP quits working when you deplete the dopamine neurotransmitter molecules.

depletes

Food and Nutrients in Disease Management (CRC Press, 2009)

Marty Hinz, MD Depression in I. Kohlstadt (ed.)

IV: PHARMACOLOGY:

A. 5-HTP aka 5HTP or 5 HTP, L-dopa aka dopa, and tyrosine aka L-tyrosine

Treatment of depression and ADHD, as well as any other serotonin and dopamine monoamine neurotransmitter diseases, is not possible through the direct administration of serotonin and dopamine monoamine neurotransmitter peripherally. This is due to the fact that the serotonin and dopamine monoamine neurotransmitter levels do not cross the blood brain barrier, as depicted in figure 1. The only way to increase the serotonin and dopamine levels of central nervous system serotonin and dopamine monoamine neurotransmitter molecules is to provide 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa, which cross the blood brain barrier and are synthesized into their respective serotonin and dopamine neurotransmitter products of synthesis by pre-synaptic serotonin and dopamine neurons.^6,7

Figure 1: The monoamine neurotransmitter molecules of serotonin, dopamine, norepinephrine, and epinephrine do not cross the blood brain barrier therefore peripheral administration of serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter levels will not increase the central nervous system serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter levels. The serotonin and dopamine neurotransmitter precursors of the serotonin, dopamine, norepinephrine, and epinephrine 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa do cross the blood brain barrier. The only way to increase central nervous system serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter levels is through administration of 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa.

B. REUPTAKE INHIBITOR DEPLETION OF SEROTONIN AND DOPAMINE MONOAMINES

The National Institute of Drug Abuse presents a detailed discussion on its website on how serotonin and dopamine reuptake inhibitor depression and ADHD drugs deplete serotonin and dopamine neurotransmitter levels. Serotonin and dopamine reuptake inhibitor drugs used to treat depression, ADHD, etc. are not the only drugs that block serotonin and dopamine reuptake; cocaine and amphetamines block serotonin and dopamine neurotransmitter reuptake as well. Serotonin and dopamine reuptake inhibitor depression and ADHD drugs block the uptake of the serotonin and dopamine neurotransmitter molecules back into the pre-synaptic neuron. In doing so, synaptic levels of serotonin and dopamine neurotransmitter molecules are increased. As synaptic serotonin and dopamine neurotransmitter levels rise, relief of depression and ADHD symptoms is observed.

Monoamine Oxidase (MAO) and the Catecholamine O-Methyl Transferase (COMT) enzymes metabolize serotonin, dopamine, norepinephrine, and epinephrine. The monoamine neurotransmitter molecules serotonin, dopamine, norepinephrine, and epinephrine are relatively stable and are not metabolize until the serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules come in contact with the MAO and COMT enzymes. When the serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules are in the vesicles of the pre-synaptic neuron, the serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules are not exposed to metabolism by the MAO and COMT enzymes; the serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules are safe and stable. When the serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules is in the synapse between the pre-synaptic and post-synaptic neuron, serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules are exposed to enzymatic metabolism, which leads to the depletion of the serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules if proper levels of balanced 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa are not administered to compensate for this process.²⁴

In depressed and ADHD patients, synaptic serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter levels are not high enough to prevent disease symptoms such as depression, ADHD, etc., as illustrated in figure 2. Treatment with serotonin and dopamine reuptake inhibitor depression and ADHD drugs leads to a decrease in presynaptic serotonin and dopamine neurotransmitter levels (where they are safe from enzymatic metabolism) and an increase in the number of serotonin and dopamine neurotransmitter molecules in the synapse, as illustrated in figure 2. The blocking of serotonin and dopamine neurotransmitter reuptake increases synaptic levels of serotonin and dopamine and the probability that serotonin and dopamine neurotransmitter molecules will experience enzymatic metabolism.

serotonin dopamine neurotransmitter deplete reversed by 5-HTP tyrosine L-dopa

Figure 2: Titled: “The effects of serotonin an dopamine reuptake inhibitor drugs on serotonin an dopamine neurotransmitter levels, serotonin and dopamine reuptake inhibitor depression and ADHD drugs may deplete neurotransmitter levels.” In the left picture, prior to treatment, serotonin or dopamine neurotransmitter levels are not high enough to prevent symptoms of depression and ADHD disease. In the center picture, serotonin and dopamine reuptake is blocked, serotonin or dopamine neurotransmitter molecules move from the vesicles of the pre-synaptic neuron to the synapse. In the right picture, the serotonin or dopamine neurotransmitter molecules are depleted, the increase in synaptic serotonin or dopamine neurotransmitter levels results in an increase in MAO and COMT metabolism. Source of picture: The National Institute of Drug Abuse.

With regards to figure 2, the net effect of enzymatic metabolism is the depletion of serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter levels in the central nervous system. The serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules do not cross the blood brain barrier. Therefore, the only way to increase central nervous system levels of serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules or to prevent the overall depletion of serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter levels when administering prescription drugs that block serotonin or dopamine neurotransmitter reuptake is to provide balanced 5-HTP aka 5HTP or 5 HTP, L-dopa aka dopa, and tyrosine aka L-tyrosine, which are then synthesized into serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter molecules. Administering L-tyrosine aka L-tyrosine (not phenylalanine or n-acetyl-tyrosine aka L-tyrosine) or L-dopa aka dopa is the only way to predictably raise dopamine, norepinephrine, and epinephrine. Administering tryptophan or 5-hydroxytryptophan (5-HTP aka 5HTP or 5 HTP) is the only way to predictably raise serotonin levels in the central nervous system. It is noted that 5-HTP aka 5HTP or 5 HTP, L-dopa aka dopa and tyrosine aka L-tyrosine are available in the United States without a prescription. The ability of tryptophan to raise serotonin levels is limited because it is a rate-limited reaction.

The effects of serotonin, dopamine, norepinephrine, and epinephrine neurotransmitter depletion by depression and ADHD drugs may have far ranging implications. It has been found in studies that depletion of serotonin by drugs may also lead to a reduction the number of serotonin synapses in the hippocampus.⁴³

raise

THE WAY TO RAISE SEROTONIN AND DOPAMINE NEUROTRANSMITTER LEVELS

SEROTONIN: Administering tryptophan or 5-hydroxytryptophan (5-HTP aka 5HTP or 5 HTP or 5HTP) is the only way to predictably raise serotonin neurotransmitter levels in the central nervous system. However, the ability of tryptophan to raise serotonin neurotransmitter levels is limited because it is a rate limited reaction.

DOPAMINE: Administering L-tyrosine aka L-tyrosine or L-dopa aka dopa is the only way to predictably raise dopamine, norepinephrine, and epinephrine neurotransmitter levels. Phenylalanine and N-acetyl-tyrosine aka L-tyrosine do not predictably raise neurotransmitter levels because they are too far up the pathway that produces these catecholamines, which means that they can be shuttled to other pathways when needed.

dopadeplete

5-HTP aka 5HTP or 5 HTP DEPLETES DOPAMINE

Using only 5-HTP aka 5HTP or 5 HTP without properly balanced L-dopa aka dopa or tyrosine aka L-tyrosine being simultaneously administered is, "Just plain wrong" As noted in the article in this section use of improperly balanced or only 5-HTP aka 5HTP or 5 HTP inhibits dopamine neurotransmitter synthesis. If you work with these 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa and do not understand how these neurotransmitter interactions occur and how to manage them properly you are doing your patient no service and may actually be doing them harm by depleting neurotransmitter levels of systems.

In the second illustration below are results with profound implications. Under normal circumstances taking only 5-HTP aka 5HTP or 5 HTP as shown in this study decreases dopamine neurotransmitter synthesis by over 50% and is very effective at depleting dopamine neurotransmitter levels. Proper balance of serotonin and dopamine neurotransmitter precursors are needed not only for optimal depression, ADHD, etc. treatment results, proper balance is needed to prevent depletion of serotonin or dopamine neurotransmitter levels with administration of L-dopa aka dopa or 5-HTP aka 5HTP or 5 HTP respectively.

Full Text Version of Article

THE EFFECTS OF 5-HYDROXYTRYPTOPHAN (5-HTP aka 5HTP or 5 HTP or

5HTP) AND 5-HYDROXYTRYPTAMINE (5-HT) ON DOPAMINE

SYNTHESIS AND RELEASE IN RAT BRAIN STRIATAL SYNAPTOSOMES

DAVID W . ANDREWS, ROBERT L PATRICK and JACK D. BARCHAS

Nancy Pritzker Laboratory of Behavioral Neurochemistry, Department of Psychiatry and Behavioral

Sciences. Stanford University School of Medicine. Stanford, CA 94305, U.S.A.

(Received 19 April 1977. Accepted 3 August 1977)

Abstract-The effects of 5-hydroxytryptophan (5-HTP aka 5HTP or 5 HTP or 5HTP) and serotonin (5-HT) on dopamine neurotransmitter synthesis and release in rat brain striatal synaptosomes have been examined and compared to the effects of tyramine and the neurotransmitter dopamine. Serotonin inhibited dopamine neurotransmitter synthesis from tyrosine aka L-tyrosine, with 25% inhibition occurring at 3 micromols-5-HT and 60% inhibition at 200 micromols. Dopamine neurotransmitter synthesis from DOPA was also inhibited by the neurotransmitter serotonin (5-HT), with 30% inhibition occurring at 200 micromols. At 200 micromols, dopamine neurotransmitter synthesis from both tyrosine aka L-tyrosine and DOPA was inhibited about 70%. When just the tyrosine aka L-tyrosine hydroxylation step was measured in the intact synaptosome, 5-HT, 5-HTP aka 5HTP or 5 HTP, tyramine and the neurotransmitter dopamine all caused significant inhibition, but only dopamine inhibited soluble tyrosine aka L-tyrosine hydroxylase 3-monooxygenase; Tyrosine aka L-tyrosine, tetrahydropteridine oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.21 prepared from lysed synaptosomes. Particulate tyrosine hydroxylase was not inhibited by 10 micromols but was about 20% inhibited by 200 micromols 5-HTP aka 5HTP or 5 HTP. At 200 micromols both 5-HT and 5-HTP aka 5HTP or 5 HTP stimulated endogenous dopamine neurotransmitter release. These experiments suggest that exposure of dopaminergic neurotransmitter neurons to 5-HT or 5-HTP aka 5HTP or 5 HTP leads to an inhibition of dopamine neurotransmitter synthesis, mediated in part by an intraneuronal displacement of dopamine neurotransmitter levels from vesicle storage sites, leading to an increase in dopamine-induced feedback inhibition of tyrosine aka L-tyrosine hydroxylase. and in part by a direct inhibition of DOPA decarboxylation.

5-HTP depeltes neurotransmitter dopamine if tyrosine 5-HTP L-dopa

Ldopa

L-dopa aka dopa DEPLETES SEROTONIN IN THE BRAIN

Based on clinical experience, research, and statistical data base analysis we have been saying for almost 10 years now “administration of only L-dopa aka dopa or improperly balanced L-dopa aka dopa depletes serotonin neurotransmitter levels and administration of only 5-HTP aka 5HTP or 5 HTP or improperly balanced 5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels.” The illustration below is from a literature article published in 2007. It studies the effects of L-dopa aka dopa administration on serotonin neurotransmitter levels in six areas of the brain.

ARTICLE CITED HERE: Long-Term L-dopa aka dopa Treatment Causes Indiscriminate Increase in Dopamine Neurotransmitter Levels at the Cost of Serotonin Neurotransmitter Synthesis in Discrete Brain Regions of Rats Cell Mol Neurobiol (2007) 27:985–996 Anupom Borah Æ Kochupurackal P. Mohanakumar

Article Full Text

L-dopa depletes neurotransmitter sertonin if 5-HTP tyrosine L-dopa

Based on clinical evidence we have been saying for years, "Use of only or improperly balanced L-dopa aka dopa depletes serotonin neurotransmitter levels, and use of only or improperly balanced 5-HTP aka 5HTP or 5 HTP depletes dopamine neurotransmitter levels." L-dopa aka dopa and 5-HTP aka 5HTP or 5 HTP needs to be used in proper balance, plus when using L-dopa aka dopa proper levels of L-tyrosine aka L-tyrosine (N-acetyl-tyrosine aka L-tyrosine and phenylalanine do not work) need to be used to stabilized dopamine neurotransmitter levels. The article above is one of the best pieces of work we have seen showing how use of only L-dopa aka dopa depletes serotonin neurotransmitter levels.

Use of unbalanced 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa precursors can deplete neurotransmitter levels.

SEROTONIN: Administering tryptophan or 5-hydroxytryptophan (5-HTP aka 5HTP or 5 HTP or 5HTP) is the only way to raise serotonin neurotransmitter levels in the central nervous system. However, the ability of tryptophan to raise serotonin neurotransmitter levels is limited because it is a rate limited reaction.

DOPAMINE: Administering L-tyrosine aka L-tyrosine or L-dopa aka dopa is the only way to predictably raise dopamine, norepinephrine, and epinephrine neurotransmitter levels. Phenylalanine and N-acetyl-tyrosine aka L-tyrosine do not predictably raise levels because they are too far up the pathway that produces the dopamine, which means that they can be shuttled to other pathways when needed.

AAdeplete

SEROTONIN, DOPAMINE NOREPINEPHRINE AND EPINEPHRINE NEUROTRANSMITTER DEPLETION DUE TO 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa

PERSPECTIVE

The same enzyme catalyzes the conversion of 5-HTP aka 5HTP or 5 HTP to serotonin and L-dopa aka dopa to dopamine. The L-amino acid decarboxylase enzyme is also known as 5-HTP aka 5HTP or 5 HTP decarboxylase or L-dopa aka dopa decarboxylase. The implications of this fact are profound.

If you start loading only 5-HTP aka 5HTP or 5 HTP or L-dopa aka dopa into the system, they can decrease dopamine neurotransmitter production or serotonin neurotransmitter production respectively. From a clinical standpoint, what does this look like?

L-dopa aka dopa has been used for a long time in the treatment of Parkinsonism since dopamine neurotransmitter molecules do not cross the blood brain barrier. L-dopa aka dopa is able to cross the blood brain barrier and is freely synthesized into dopamine without biochemical feedback regulation. Long-term loading of L-dopa aka dopa without the use of 5-HTP aka 5HTP or 5 HTP leads to depletion of serotonin neurotransmitter levels one of the causes of this is that L-dopa aka dopa competitively inhibits 5-HTP aka 5HTP or 5 HTP at the general decarboxylase enzyme.

The medical literature lists depression as a side effect of long-term L-dopa aka dopa administration in treatment of Parkinsonism. The literature further indicates that this is a serotonin driven depression that responds to the most serotonin specific antidepressant - citalopram (Celexa or Lexapro). The real problem is that unopposed L-dopa aka dopa use has depleted serotonin neurotransmitter levels to the point that depression develops.

The synthesis of serotonin and dopamine is illustrated in to the right. Peripheral administration of only 5-HTP aka 5HTP or 5 HTP or only L-dopa aka dopa will decrease the synthesis of the other system (dopamine or serotonin respectively). With administration of only one precursor of 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, or L-dopa aka dopa, the administered precursor dominates the enzyme and compromises proper synthesis of the other system’s neurotransmitter levels through competitive inhibition. This is due to the fact that the same enzyme catalyzes the conversion of 5-HTP aka 5HTP or 5 HTP to serotonin and L-dopa aka dopa to dopamine.

SYNTHESIS COMPETITION

neurotransmitter serotonin dopamine synthesis from tyrosine L-dopa 5-HTP

The aromatic L-amino acid decarboxylase enzyme is also known as 5-HTP aka 5HTP or 5 HTP decarboxylase enzyme or L-dopa aka dopa decarboxylase enzyme, as well as the general decarboxylase enzyme. The implications of this fact are profound.The administration of only 5-HTP aka 5HTP or 5 HTP or L-dopa aka dopa will compete with and inhibit the synthesis of the opposite precursor (dopamine and serotonin respectively) at the enzyme.

In Parkinson patients, the long-term administration of L-dopa aka dopa with insufficient serotonin precursors will result in depression and a host of other problems. The literature is very clear that this depression is a serotonin dependent depression, which responds optimally to the most serotonin specific reuptake inhibitor, citalopram.

METABOLISM COMPETITION

MAO metabolizes the neurotransmitters serotonin and dopamine made from tyrosine L-dopa 5-HTP

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 or dopamine levels are increased with administration of 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine or L-dopa aka dopa, enzymatic activity also increases.

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

UPTAKE COMPETITION

In order for the synthesis of the monoamine neurotransmitter molecules to occur, the precursors 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa 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 transporter type 1” (OCT) found in the proximal convoluted renal tubule cells are a prototype for 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa uptake, see the illustration below.

Neurotransmitter molecules synthesis by the kidneys from L-dopa aka dopa and 5-HTP aka 5HTP or 5 HTP is the source of urinary serotonin and catecholamines. Serotonin and dopamine are synthesized by the kidneys, then excreted into the urine or secreted into the system. Uptake is affected by administration of a single unbalanced precursor such as 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, or L-dopa aka dopa or improperly balanced 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, or L-dopa aka dopa which may overwhelm and compete with uptake of the other 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa. Administration of only L-dopa aka dopa inhibits uptake of 5-HTP aka 5HTP or 5 HTP. Administration of only 5-HTP aka 5HTP or 5 HTP has the same effect on L-dopa aka dopa uptake.

serotonin dopamine neurotransmitter synthesis sites from tyrosine L-dopa 5-HTP

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

neurotransmitters serotonin and dopamine synthesis from L-dopa 5-HTP tyrosine

From a clinical standpoint, long-term use of L-dopa aka dopa becomes ineffective as the serotonin is depleted. In order to regain control of symptoms when L-dopa aka dopa quits working, 5-HTP aka 5HTP or 5 HTP needs to be started. But this has not been the standard approach in medicine. In medicine when the L-dopa aka dopa quits working the approach is to increase the L-dopa aka dopa dosing which depletes serotonin even more.

These same observations are also true when only 5-HTP aka 5HTP or 5 HTP is used in treatment. Over time, 5-HTP aka 5HTP or 5 HTP depletes dopamine, norepinephrine, and epinephrine levels. Eventually, when dopamine levels drop low enough, 5-HTP aka 5HTP or 5 HTP becomes ineffective and the side effects of dopamine, norepinephrine, and epinephrine depletion occur. 5-HTP aka 5HTP or 5 HTP and L-dopa aka dopa must be provided in proper balance for optimal results. For years doctors have depleted serotonin levels in Parkinson patients by prescribing only L-dopa aka dopa with no 5-HTP aka 5HTP or 5 HTP and when the problems of serotonin depletion occurred to include the L-dopa aka dopa no longer working, depression and a host of other problems these doctors did not know what they were looking at and simply increased the L-dopa aka dopa dosing making the real cause of the problem worse, "serotonin depletion from L-dopa aka dopa."

how

How Reuptake inhibitor drugs Deplete Neurotransmitter Levels

A list of reuptake inhibitor drugs is found at the top of this web page on the right.

Pictures from, "The National Institute of Drug Abuse"

serotonin or dopamine neurotransmitter synapse increased by 5-HTP tyrosine L-dopa

For depressed patients, synaptic neurotransmitter levels are below the levels needed to prevent disease (depression, ADHD, etc.) symptoms.

serotonin and dopamine uptake inhibitors move neurotransmitters 5-HTP L-dopa tyrosine

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

neurotransmitter serotonin and dopamine reuptake inhibitors reversed by 5-HTP tyrosine L-dopa

Overtime, the net effect of enzymatic metabolism is the depletion of neurotransmitter levels in the central nervous system. The neurotransmitter molecules do not cross the blood brain barrier. Therefore, the only way to increase central nervous system levels or to prevent the overall depletion of neurotransmitter levels is to provide properly balanced 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa precursors, which cross the blood brain barrier and are able to be synthesized into the neurotransmitter molecules in the CNS.

Drugs that work with neurotransmitter levels, do not work if there are not high enough neurotransmitter levels with which to work. Long term use of antidepressants depletes neurotransmitter levels in most patients if proper levels of balanced 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa are not administered.

The monoamine neurotransmitter molecules (serotonin, dopamine, norepinephrine, and epinephrine) will not cross the blood brain barrier. The only way to increase central nervous system neurotransmitter levels is to provide 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa which cross the blood brain barrier. They will then be synthesized in the brain into new neurotransmitter molecules.

If you keep the system topped off with 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa, antidepressants and other drugs that work with neurotransmitter levels will function optimally and patients will feel optimal.

workopt

USING 5-HTP aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa aka dopa TO KEEP DRUGS WORKING

dopamine and serotonin neurotransmitter kept working with 5-HTP tyrosine L-dopa

tip

TIP OF THE ICEBERG

Early on in this research project (started in 1997) Dr. Uncini hospital based laboratory pathologist suggested that what we were looking at with the kidneys was just the "tip of the iceberg" and that the balance and interaction of th