Neurotransmitters by Ray Sahelian, M.D.

Definition of a Neurotransmitter
A neurotransmitter is defined as a chemical messenger which is released from the synaptic terminal of a neuron at a chemical synapse that diffuses across the synaptic cleft and binds to and stimulates the post-synaptic membrane. In simple words, a neurotransmitter is a chemical messenger released from one nerve cell which makes its way to another nerve cell where it influences a particular chemical reaction to occur. Neurotransmitters contro major body functions including movement, emotional response, and the physical ability to experience pleasure and pain.

The neurotransmitters that are most familiar to the public are serotonin, norepinephrine, dopamine, acetylcholine, and GABA.

Types of Neurotransmitters
Neurotransmitters can be broadly classified into several categories:
Small molecule transmitters and neuroactive peptides. Around 10 small-molecule neurotransmitters are generally recognized: acetylcholine, 5 amines, and 3 or 4 amino acids,
Purines, (Adenosine, ATP, GTP and their derivatives).
Fatty acids
Neuroactive peptides have been found, among them neuropeptide Y and hormones such as leutenizing hormone.
Single ions, such as the mineral zinc are considered neurotransmitters by some.
Gases such as nitric oxide

Serotonin Neurotransmitter
Serotonin happens to be the most widely studied neurotransmitter since it helps regulate a vast range of psychological and biological functions. Serotonin (5-hydroxytryptamine or 5-HT) was first identified in 1948. The wide array extent of psychological functions regulated by serotonin involves mood, anxiety, libido, aggression, and thinking abilities. Other brain neurotransmitters, such as dopamine and norepinephrine, also influence mood and arousal. However, serotonin generally has different effects. For instance, excess amounts of serotonin cause relaxation, sedation, and a decrease in sexual drive. Prozac, a common antidepressant of the SSRI type, elevates serotonin levels in the brain. One of the common side effects of SSRIs is diminished sexual urge and sensation. There is a nutrient called 5-hydroxytryptophan (5-HTP) that is the immediate precursor to serotonin. When ingested as a supplement, 5-HTP converts in the brain into serotonin. The substance 5-HTP is often used to treat depression and anxiety. I have noticed that 5-HTP supplements decrease sexual interest.

Dopamine neurotransmitter
Dopamine is one of the most important neurotransmitters involved in the human sexual response. Dopamine has a significant effect on sexual desire. Plus, elevation of dopamine levels often leads to an improvement in mood and alertness. A number of psychiatric disorders, particularly Parkinson's disease and mood disorders, are attributed to imbalances in dopamine levels. Dopamine is made from the amino acid tyrosine. Once produced, dopamine can, in turn, convert into the brain chemicals norepinephrine and epinephrine. Some of the natural supplements that increase dopamine levels include NADH and CDP-choline.

Acetylcholine neurotransmitter
Acetylcholine was the very first neurotransmitter to be identified back in the early 1900s. It is made simply from choline, a natural substance found in lecithin, and a two-carbon molecule called acetyl. Acetylcholine plays numerous roles in the nervous system. In the brain, acetylcholine is involved in learning and memory whereas in the genital organs, acetylcholine is released by the parasympathetic nerves. Acetylcholine helps in the release of nitric oxide, which leads to the relaxation of smooth muscles and engorgement of the genital organs. Nutrients that elevate levels of acetylcholine include choline and CDP-choline.

Norepinephrine neurotransmitter and Epinephrine
In the flaccid state of the penis, frequent release of norepinephrine from sympathetic nerves contracts the arteries in the penis and also contracts the smooth muscles of the corpora cavernosum. Therefore, in the normal state, norepinephrine keeps the penis soft. A relative predominance of norepinephrine-induced contraction over nitric oxide-mediated relaxation may contribute to erectile dysfunction. Two amino acids phenylalanine and tyrosine, sold as supplements, are converted into dopamine. Dopamine, in turn, is converted into norepinephrine, and then epinephrine. The ingestion of these amino acids elevates dopamine and norepinephrine levels, and hence will lead to alertness and mood elevation and increased sexual interest. However, excess amounts of norepinephrine and epinephrine may make it difficult to have erections. In addition, high amounts raise blood pressure, increase heart rate, and cause anxiety, irritability, and insomnia. Yohimbe, the natural sex booster from Africa, facilitates erections by blocking the inhibitory action of norepinephrine on the penis.

Nitric Oxide: Say Yes to NO
Nitric oxide (NO) is the most important neurotransmitter involved in the engorgement of genital organs leading to erections. I will mention NO several times Throughout this book, since some you will find herbs and nutrients that help in the formation of this chemical. For instance, the amino acid arginine can be metabolized into NO by an enzyme known as nitric oxide synthase. This conversion is done in endothelial cells, which are cells that line the inside of blood vessels. Ginseng, the popular herbal aphrodisiac, is also thought to increase NO levels. NO functions by activating an enzyme called guanylate cyclase. Guanylate cyclase, in turn, helps form cyclic guanosine monophosphate (cGMP). cGMP becomes the secondary messenger that causes smooth muscle relaxation, resulting in venous engorgement and erections. Under normal conditions, cGMP helps the smooth muscles surrounding the arteries of the penis and the smooth muscles of the corpus cavernosum to relax. This allows blood to easily flow into the penis. Any condition that interferes with the signaling of these messenger enzymes can quickly lead to the breakdown of the entire process and cause erectile dysfunction. Viagra works by blocking an enzyme that breaks down cGMP, hence more of this chemical is left to help dilate the genital arteries. Interestingly, having adequate levels of androgen hormones in the body makes it easier for the genital organs to respond to nitric oxide.
     Nitric oxide is a biological messenger molecule produced by one of the essential amino acids L-arginine by the catalytic action of the enzyme NO synthase (NOS). The dual role of nitric oxide as a protective or toxic molecule is due to several factors, such as; the isoform of NOS involved, concentration of NO and the type of cells in which it is synthesised, the availability of the substrate L-arginine, generation of guanosine 3,5'-cyclic monophosphate (cGMP) from soluble guanylate cyclase and the overall extra and intracellular environment in which nitric oxide is produced.

GABA neurotransmitter
In the adult central nervous system (CNS), gamma-amino butyric acid (GABA) is a predominant inhibitory neurotransmitter, and is involved in relaxation. Thus, dysfunction of the GABA system is implicated in the pathophysiology of several neuropsychiatric disorders, including anxiety and depression.
     In mammals, 16 different polypeptides (alpha1-alpha6, beta1-beta3, gamma1-gamma3, delta, epsilon, pi, and theta) have been identified, using recombinant DNA techniques, each of which is encoded by a distinct gene. The products of these genes assemble in diverse combinations to form a variety of receptor subtypes that have different sensitivities to a number of clinically relevant compounds, such as the benzodiazepines (BZs). 2. Based on a number of chromosomal mapping techniques, the majority of the GABA(A) receptor genes have been localized, in man, in four clusters on chromosomes 4, 5, 15, and the X. Furthermore, the genes that are present within these clusters have a conserved transcriptional orientation. It has, therefore, been proposed that the clusters arose largely as a consequence of two whole-genome doublings that occurred during chordate evolution, and that the ancestral cluster contained an "alpha-like," a "beta-like," and a "gamma-like" subunit gene.
     Piracetam is a derivative of GABA. Supplements of GABA are also available, however it is unclear how effectively a GABA supplement can cross the blood brain barrier.

Glutamate neurotransmitter
The role of glutamate receptors in synaptic transmission and excitotoxicity in the nervous system is well established. Recent evidence has emerged that glutamatergic mechanisms also exist in a wide variety of non-neuronal cells. In the case of thymocytes and lymphocytes, several types of glutamate receptor are expressed which can induce functional changes. Glutamate may serve as a signaling agent between the immune and nervous systems.

Histamine neurotransmitter
Histamine has many actions in both the periphery and in the central nervous system. In the lungs, histamine acts the smooth muscle of the smaller bronchioles to cause constriction, and reduced air flow. In the stomach, histamine is involved in acid secretion.

Neurotransmitter testing
A neurotransmitter test is available to measure the levels of major neurotransmitters including serotonin, norepinephrine, epinephrine, GABA and dopamine. This testing can be done by urine, blood, or a spinal tap to measure neurotransmitter levels in the spinal fluid. However, only in rare cases is it necessary to do neurotransmitter testing. Even if we know the blood level of these neurotransmitters, and we find a neurotransmitter deficiency, it offers little help in guiding therapy since neurotransmitter levels and neurotransmitter production fluctuates easily from day to day and hour to hour. Neurotransmitter testing is not a reliable way to determine how a person will respond to a particular medicines or supplement for conditions such as depressions, anxiety, ADHD, etc. Neurotransmitter testing could reveal a neurotransmitter imbalance that would be accurate for that particular time period only. Neurotransmitter testing is appropriate in cases of neurotransmitter imbalance or excess such as pheochrmocytoma and other clear cut medical conditions.
 

Monoamine neurotransmitter
These include serotonin, norepinephrine, GABA, glutamate, and dopamine. The monoamine hypothesis holds that mood disorders are caused by a depletion in one or more of these neurotransmitters.

Neurotransmitter metabolism
The process by which our bodies make, use, and break down neurotransmitters is extremely complicated. When there is a disruption within this process, abnormalities can occur in any of their essential functions.

Acetylcholine is derived from Choline
Serotonin [5-Hydroxytryptamine (5-HT)] is derived from  Tryptophan
GABA is derived from Glutamate
Histamine is derived from Histidine
Epinephrine, norepinephrine and dopamine are derived from Tyrosine
Adenosine is derived from ATP
Nitric oxide is derived from Arginine


Neurotransmitter release
Neurotransmitters are responsible for transmitting information across the synaptic gap between neurons. Neurotransmitters are stored in synaptic vesicles. When action potentials are conducted down an axon, synaptic vesicles attach themselves to the presynaptic membrane, then break open and spill neurotransmitter into the synaptic cleft. Neurotransmitters in the synaptic cleft attach to postsynaptic receptor sites and trigger an action potential in the postsynaptic membrane.  Some neurotransmitters attach to presynaptic neurotransmitter receptors (autoreceptors) located on the membrane (pre-synaptic membrane) of the cell that originally released them.