L-Dopa: Effects, Side Effects, And Dosages

L-Dopa: Effects, Side Effects, And Dosages November 3, 2017


Dopamine is classified as a neurotransmitter. Its main focus, at least in brain activity, is to control the pleasure and reward centers of the brain. However, the dopamine is also essential in regulating not only emotional responses, but also movement. Its functions are important not only in providing what many humans describe as “reward” responses and sensations, but also the actions that a person can take to achieve those positive emotional responses.

Dopamine and dopamine supplements like L-Dopa focus on neurochemistry. Therefore, dopamine has a huge impact not only on how we feel, but also on how we behave and react to certain circumstances. Dopamine gives humans the ability to think, to process, to plan ahead, and resist negative impulses.

The basic definition of dopamine is that it’s a neurotransmitter that controls a number of communication pathways in the brain. Dopamine is responsible for instructing neurons to transmit signals, modulate those signals, or cease transmission of those signals.

Dopamine, as a neurotransmitter, is also known as a catecholamine. Catecholamines are often described as a specific chemical group that is attached to an amine.

Dopamine is mainly ingested by the foods we eat. It is not manufactured in the brain. Dopamine is manufactured from a protein amino acid called tyrosine. Tyrosine is manufactured through another amino acid, phenylalanine. Tyrosine develops into dopamine through enzyme activities of tyrosine hydroxylase. Dopa or l-dopa is an essential nutritional supplement that becomes dopamine through the action of a chemical known as dopa decarboxylase. Norepinephrine, another neurochemical found in the brain, can also be converted into dopamine, depending on a number of chemical reactions.

Dopamine cannot cross the blood-brain barrier, although serotonin, (precursor tryptophan) as well as tyrosine can. In other words, the brain requires dopamine, but it’s manufactured through a number of precursors. L-dopa supplements may be very beneficial in providing the body with the chemical components required to provide dopamine.

The basic function of dopamine in the brain is to provide motivation. Dopamine has also been scientifically associated with a number of body functions in addition to brain function, including metabolism. L-dopa is a supplementary chemical substance that is required in normal biological processes by humans and other mammals, as well as a number of plants.

Things To Know

  • Synthetically developed L-dopa is known by several other names, including Levodopa (a popular drug), 4-dihydroxyphenylalanine, and L-3. As a precursor to the dopamine, norepinephrine, and epinephrine (adrenaline) neurotransmitters, it has the ability to mediate neurotrophic factors of the central nervous system and the brain.
  • Levodopa, a brand drug is known by additional names including Sinemet, Prolopa, and Atamet, among others, is often used as a clinical treatment for various stages of Parkinson’s disease as well as a condition known as a dopamine-responsive dystonia.
  • Deficiencies in dopamine are most noted in individuals diagnosed with Parkinson’s disease.
  • Deficiencies in dopamine may also potentially increase the risk of addictive behaviors (1). This is because some types of dopamine receptors are associated with or linked to individuals who are thrill seekers or sensation seekers, and in many cases, are known as risk-takers.
  • Some scientific research has suggested that a person’s dopamine levels are involved in prenatal neurochemical development, at least in how it functions in the brain (2).
  • The impact of dopamine and where it’s located in the brain can also have an impact on how any individual thinks, rationalizes, and behaves. For example, consider the brain. It’s divided into two hemispheres. The left brain is responsible for knowledge functions such as reasoning, language skills, and learning. The bright side of the brain is more creative and intuitive, and, at its most basic definition, enables us to rationalize when it comes to intuition, as well as help develop the way we speak and learn and hone music, writing, or other creative skills.
  • The human brain is composed of approximately 100 billion neurons, but only 20,000 of them may contain dopamine (3). L-dopa has the capability of passing through the blood-brain barrier, while dopamine cannot.

Brief History Of L-Dopa Research

L-dopa (amino acid L-3 or 4-dihydroxyphenalanine), which was first synthesized from its DL “racemate”, was identified in 1911(4). Racemate is defined as the conversion of a pure mixture with one enantiomer [optical isomer or molecular pair that is not a mirror image of each other, that one can superimpose one on top of another] into one where more than one enantiomer is present. The term racemization is often used to imply results of a mixture where D and L enantiomers are present in quantities that are equal in measure. Since the 1960s, L-dopa has been noted to be the most beneficial (to date) treatment when it comes to Parkinson’s disease.

In 1913, it was reported to come from legumes, initially thought to be inactive, at least biologically. Later studies in the late 1920s and early 1930s determined that at least in small animals (rabbit), DL-dopa had a rather significant impact on the metabolism of glucose as well as blood pressure (arterial).

Ever since then, the biological mechanisms of action of L-dopa have been studied. In the late 1930s, the first experimental development of L-dopa was demonstrated in humans as well as animals regarding the enzymatic conversion from the enzyme L-dopa decarboxylase to L-dopa and then dopamine.

Studies continued in the 1940s (human and animal), with focus on the potential of L-dopa/dopamine to have an effect on the vascular blood pressure. By the 1950s, the focus transitioned to brain catecholamines and its effect on the basal ganglia.

In the 1960s, it was noted that deficiencies of dopamine in the brain were associated with Parkinson’s disease, as well as its powerful therapeutic effect on that disease. By the late 1960s, high doses of L-dopa taken in daily regimens were the norm in clinical practices in the treatment of Parkinson’s. Today, L-dopa continues to be one of the traditional and most beneficial uses when it comes to neurotransmitter replacement therapy.

Studies continue regarding the effect of dopamine on the central nervous system, by itself and as part of other biological activities.

Chemical Structure


or by its chemical formula: C8H11NO2.

Dopamine is also known as:

  • 4-(2-Aminoethyl)benzene-1,2-diol
  • Hydroxytyramin
  • Oxytyramine
  • 3-Hydroxytyramine
  • Intropin (a discontinued drug)
  • Dopamine Hydrochloride (a discontinued drug)
  • 3,4 Dihydroxyphenethylamine

Mechanism Of Action

Dopamine is classified as a catecholamine formed by the decarboxylation of dihydroxyphenylalanine. It is a precursor of epinephrine and norepinephrine. Dopamine binds to alpha- and beta-1 adrenergic receptors. When mediated by myocardial beta-1 adrenergic receptors (for heart function) dopamine can increase both heart rate as well as force, contributing to enhanced cardiac output. The alpha-1 adrenergic effect on receptor stimulation acts on smooth muscle vasculature (such as blood vessel walls) and initiates vasoconstriction for increased systemic resistance.

Dopamine is also important in stimulating the dilation of renal blood vessel walls, increasing renal blood flow, improving glomerular filtration (a process that affects kidney function and the volume and rate at which blood passes through the glomerulus capillaries). The glomerulus is a cluster of capillaries located at the end of kidney tubules, the location where wastes and waste products are filtered out of the blood and excreted in urine. It’s also important in the excretion of sodium from the body as well as urine output.

While dopamine is frequently used in the treatment of cardiac issues such as decreased cardiac output and blood pressure, it’s also often used during CPR (5).

Dopamine is strongly associated with mental health issues such as depression, schizophrenia, and mania depending on either high or low levels. As a monoamine, common dopamine (DA) is also involved in:

  • Fine muscle movements (i.e. Parkinson’s)
  • Integration of thoughts and emotions
  • Decision-making processes
  • Responsible for stimulating the hypothalamus to release hormones (thyroid, adrenal, sex)

Dopamine transmitters are associated with five receptors:

D1 – mid-brain, GABA terminals- most abundant CNS receptor that stimulates AC (adenylyl cyclase) (6).
D2 – basal ganglia – inhibits AC, plays a role in potassium channel activation, and release of arachidonic acid potentiation.
D3 – currently under study, but believed to have a mediatory effect on the influence of regulatory Da on neurotensin production.
D4 – found in the hippocampus and frontal cerebral cortex regions of the brain
D5 – also stimulates AC and is believed to impact the pain stimuli.

Dopamine receptors are either D1-like or D2-like. D1-like receptors, subtyped as Gs protein, are involved in the activation of adenylyl cyclase, which converts adenosine triphosphate to cyclic adenosine monophosphate (cAMP) (7).

D2-like dopamine receptors belong to the family/group that combines with the Gi protein. It activates an alpha subunit that inhibits the conversion of adenylyl cyclase, reducing cAMP.

The limbic system, defined as a group of structures that include a portion of the frontal cortex, the brain stem, and the basal ganglia, is the locus of psychological activity. Within these areas are found the monoamine transmitters: (norepinephrine, dopamine, and serotonin), amino acid transmitters like y-aminobutyric acid (GABA), and glutamate. Neuropeptides (chemical signals in the brain) also respond to and play a huge impact on these areas of the brain. Any alterations in these areas, or in the presence of neurotransmitters, are believed to form the foundation of a number of psychiatric disease processes.

Current research has focused on the mechanisms of action of such neurotransmitters and their receptors, which, as mentioned, have been consistently associated and linked to mental activity. For example, deficiencies of serotonin or norepinephrine, sometimes both, may result in depression. Recent examination of serotonin on depression has questioned this long perceived belief (8).

In Alzheimer’s patients, it has been noted that insufficient transmission and release of transmitters or loss of ability of postsynaptic receptors to respond to transmitters can contribute to a cause and consequence effect on intracellular changes. Therefore, a number of thought disorders, including schizophrenia, have been psychologically associated with excessive transmission of the dopamine neurotransmitter (9). This can either be caused by the excess release of a transmitter or increase in receptor responsiveness.

GABA, another neurotransmitter, has been noted to play an important function in modulating or moderating the excitability of neurons that can contribute to anxiety. Anti-anxiety drugs increase the effectiveness of the GABA neurotransmitter by increasing its responsiveness receptors (10).

Basal ganglia dopamine (D2) is important in the regulation of movements. Therefore, a blockage of this form of dopamine can lead to abnormalities in motor movements such as those noted in Parkinsonism, dyskinesia, tardive dyskinesia, akathisia, and akinesia.

One of the most vital psychological functions of dopamine is that it influences the hypothalamus factors that can inhibit the release of prolactin from the anterior lobe of the pituitary gland. This blockage of transmissions of dopamine can contribute to increased secretions of prolactin from the pituitary gland. In women, this can result in a condition known as amenorrhea or absence of the menses. In men, it can contribute to the development of male breasts, known as gynecomastia.

Symptoms Of Dopamine Deficiency

The most commonly known symptom or illness that results from dopamine deficiencies are noted in those diagnosed with Parkinson’s disease. Michael J. Fox, a popular actor, has brought a great deal of attention to dopamine deficiencies due to his own diagnosis of Parkinson’s disease. Dopamine deficiencies can also contribute to:

  • Mental insufficiency or retardation (this is the case of a relatively rare hereditary disease known as PKU, often associated with mental retardation caused by a deficiency in iodine known as cretinism).
  • Attention Deficit Hyperactivity Disorder (ADHD)
  • Parkinson’s disease
  • Alzheimer’s disease
  • Bipolar conditions and disorders
  • Depression
  • Addiction or prevalence for addictive behaviors (drugs, gambling, etc.)
  • Eating behaviors such as binge eating
  • Schizophrenia

At the same time, excessive levels of dopamine in the body, especially where it doesn’t belong, has been noted to contribute to psychotic behaviors. This is noted in individuals who engage in illicit drug use. Excessive drug use can inhibit reuptake of dopamine in the brain. This is common among users of cocaine as well as methamphetamines. Because of this inability to reuptake dopamine, excessive amounts of dopamine in the bloodstream can contribute to many of the sensations linked to addictive drugs including a sense of euphoria or well-being, intense libido or sexual desire and feelings, as well as aggression.

Uses And Therapeutic Dosage Recommendations

One of the main and most popular sources of L-dopa in the form of nutritional or alternative supplement used today comes from the legume plant, Mucuna Pruriens. The plant has been used for thousands of years in traditional Ayurvedic (Indian) medicine as a treatment for a number of diseases, including the tremors associated with Parkinson’s disease.

Some research has attempted to determine the efficacy of Levodopa (L-dopa) (pharmacologically speaking) with two different doses of Mucuna pruriens preparations as compared to standard L-dopa/carbidopa medication.

This study was very small in nature and involved eight patients diagnosed with Parkinson’s disease with short duration responses to L-dopa and periodic dyskinesia (11). The study was controlled, randomized, and double-blind crossover. Patients were given single doses of 204/50 mg LD/CD and 15 and 30 g of Mucuna pruriens preparation randomly at weekly intervals.

The results of the clinical trial determined that when compared with standardized LD/CD with 30 g of Mucuna Pruriens preparations, resulted in a faster onset of effects, which was surprising in itself, but also reflected in shorter latencies to L-dopa plasma concentrations.

However, it should be noted that no differences in relation to tolerability or the dyskinesia aspects of the disease were noted. The conclusion of the study determined that the rapid action onset of Mucuna pruriens without an associated increase in dyskinesia symptoms suggest that the natural L-dopa source might possess an advantage over conventional L-dopa preparations, at least regarding the long-term management of Parkinson’s disease. However, at the time of the journal article writing (2004), more research was required regarding the long-term efficacy and tolerability.

L-dopa supplements are popular among consumers for their perceived ability to increase concentrations of dopamine in the body. For example, after L-dopa is absorbed into the central nervous system, it’s converted into dopamine. As mentioned, it’s converted with an enzyme known as dopa decarboxylase (aromatic L-amino acid decarboxylase).

Dopa decarboxylase also provides a number of functions and reactions such as its ability to catalyze:

  • L-dopa to dopamine (neurotransmitter)
  • 5HTP to serotonin or 5HT (neurotransmitter)
  • L-Histidine to histamine (neurotransmitter)
  • Phenylalanine to phenethylamine (trace amine neurotransmitter)
  • L-Tyrosine to Tyramine (trace amine neurotransmitter)
  • Tryptophan to tryptamine (trace amine neurotransmitter)

These are all important components involved in neurotransmitter activities, reactions, synthesis, and regulation. It’s important to note that catecholamines in humans and a number of trace amines are synthesized from phenylalanine, an amino acid.

All activities of the brain naturally involve activities and actions of neurotransmitters, receptors, and neurons. Each of these can be targeted for pharmacological intervention. While pharmacological intervention is often achieved with psychotropic drugs, over-the-counter supplements may also increase or decrease neurotransmitter and receptor functions and systems.

For example, while it has been concluded that hallucinatory or delusional behaviors can be the result of overactivity of dopamine and its receptors, agents effective in reducing such symptoms and behaviors must focus on specific receptors for dopamine.

A number of treatment protocols utilizing antipsychotics, mood stabilizers, anti-epileptic drugs, and antidepressants as well as benzodiazepines have been used to treat a number of psychiatric and mental health issues in the brain that directly influence dopamine, norepinephrine, epinephrine, serotonin, and GABA.

However, many antipsychotic/anti-depression drugs also have the ability to seriously affect not only mental, but also physical aspects of health and wellness.

Side Effects Of L-Dopa

L-dopa supplements do provide a number of positive effects for individuals, but it is always important to consult with the physician before taking even over-the-counter supplements, especially in the case of any emotional or mental issues or diagnoses.

Like prescription drugs, L-dopa supplements can cause a number of side effects and potential interactions with use. Of course, dosage, age, weight, and health status can have an influence on such effects. Nootropic forms of L-dopa are commonly used to relieve and reduce symptoms of depression and anxiety. They may also have a potential to improve concentration, attention or focus, as well as improving mood.

One of the main forms of L-dopa supplements from herbal extracts of Mucuna pruriens continues to be the most popular. However, the ability of herbs like Mucuna pruriens to increase dopamine levels is yet to be verified through widespread and large clinical trials and studies.

When it comes to side effects, individuals may experience different reactions. When taking the recommended dosage in supplement form, the side effects are typically minimized. Some of the more common and mild side effects associated with L-dopa supplement usage include:

  • Nausea or upset stomach
  • Headaches (often quite severe)
  • Erratic sleep or interrupted sleep cycles

Individuals diagnosed with blood pressure or cardiovascular problems may notice an increase in blood pressure, although when taken under 1 g, the side effects are often minimized.

The recommended dosage depends on why L-dopa supplements are taken. Some supplement manufacturers claim that L-dopa in a number of dosage recommendations may contribute to enhanced mood as well as a non-drug therapy to reduce Parkinson’s disease symptoms.

L-dopa is also a common supplement for improved sexual libido and health, and is also used by a number of bodybuilders and athletes to enhance the benefits of testosterone, HGH, and other prescription as well as over-the-counter supplements designed to improve muscle mass gains, physical endurance and stamina, libido, and so forth.

Dosage Recommendations

Starting dosage recommendations for L-dopa, depending on milligram strength and brand or manufacturer, are anywhere between 100 mg and 900 mg daily, divided into two or three separate doses to be taken throughout the day. New users of L-dopa are cautioned to start with the lowest dosage and gradually increase to maximum dosage.

Starting out at the lowest dosage of approximately 100 mg a day, taken at once or divided if possible, may help to reduce side effects until your body becomes accustomed to it. After a week or two, increase the dosage by increments of 100, again depending on the milligram strength and ability to split the doses. Do not split or divide pills, capsules, or tablets of L-dopa, as this may affect its efficacy, as well as cause too much L-dopa or well as other herbal ingredients to be absorbed into the bloodstream at once.

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