Serotonin advice
Serotonin was first recognised as a powerful vasoconstrictor in blood serum. It was isolated in 1948 by Page and was later found to be associated with the central nervous system.
The chemical name for serotonin is 5-hydoxytryptamine which is often abbreviated to 5-HT.
Serotonin is naturally produced in the Pineal gland which lies deep at the centre of the human brain. The average adult human possesses only 5 to 10 mg of serotonin, 90 % of which is in the intestine and the rest in blood platelets and the brain.
One role of this 'wonder drug' is as a neurotransmitter, allowing numerous functions in the human body including the control of appetite, sleep, memory and learning, temperature regulation, mood, behaviour, cardiovascular function, muscle contraction, endocrine regulation and depression. Subsequent to his discovery of Serotonin, Page commented that no physiological substance known possesses such diverse actions in the body as does serotonin.
5-HT is also found in wasp stings and scorpion venom where its function is of an irritant, since intravenous injection of serotonin in humans leads to pain, gasping, coughing, a tingling and prickling sensation, nausea, cramps and other unpleasant symptoms. Serotonin is believed to play an important part of the biochemistry of depression, migraine, bipolar disorder and anxiety. It is also believed to be influential on sexuality and appetite. The name "serotonin" is something of a misnomer and reflects the circumstances of the compound's discovery. It was initially identified as a vasoconstrictor substance in blood serum - hence "serotonin", a serum agent affecting vascular tone. This agent was later chemically identified as 5-hydroxytryptamine (5-HT) and as the broad range of physiological roles were elucidated, 5-HT became the preferred name in the pharmacological field.
Serotonin is found extensively in the human gastrointestinal tract, or gut, as well as in the blood stream. In our body, serotonin is synthesized from the amino acid tryptophan by various enzymes. Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system (CNS). This is due to the blood-brain barrier preventing serotonin in the blood stream from affecting serotonin levels in the brain. However, the amino acid tryptophan and its metabolite 5-hydroxytryptophan, from which serotonin is synthesized, are capable of crossing the blood-brain barrier. These agents are available as dietary supplements and may be effective serotonergic agents, though their efficacy is questionable. One breakdown product of serotonin is 5-hydroxyindoleacetic acid (5HIAA) which is excreted in the urine. Serotonin and 5HIAA are sometimes produced in excess amounts by certain cancer tumors, and levels of these substances may be measured in the urine to test for these tumors. 5-HT is generally thought not to be released from synaptic terminal boutons in the manner of classical neurotransmission but from serotonergic varacosities into the extra neuronal space. From here it is free to diffuse over a relatively large region of space (>20µm) and activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons. Serotonin is a neurotransmitter involved in the transmission of nerve impulses. Neurotransmitters are chemical messengers within the brain that allow the communication between nerve cells. Packets of serotonin (vesicles) are released from the end of the presynaptic cell into the synaptic cleft. The serotonin molecules can then bind to receptor proteins within the postsynaptic cell, which causes a change in the electrical state of the cell. This change in electrical state can either excite the cell, passing along the chemical message, or inhibit it. Excess serotonin molecules are taken back up by the presynaptic cell and reprocessed.
The neurons in the brain that release serotonin are found in small dense collections of neurons called Raphe Nuclei. The Raphe Nuclei are found in the medulla, pons and midbrain which are all located at the top of the spinal cord. Serotonergic neurons have axons which project to many different parts of the brain, therefore serotonin affects many different behaviors.
Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is through the specific monoamine transporter for 5-HT, 5-HT reuptake transporter, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake including MDMA, cocaine, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The pharmacology of 5-HT is extremely complex, with its actions being mediated by a large and diverse range of 5-HT receptors. A variety of psychiatric medications affect serotonin levels, including the monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), atypical antipsychotics, and the selective serotonin reuptake inhibitors (SSRIs). The MAOIs prevent the breakdown of monoamine neurotransmitters (including serotonin) and therefore increase concentrations of the neurotransmitter in the brain. MAOI therapy is associated with many adverse drug reactions and patients are at risk of hypertensive crisis triggered by foods with high tyramine-content and certain drugs. Some drugs inhibit this re-uptake of serotonin, again making it stay in the synapse longer. The tricyclic antidepressants inhibit the re-uptake of both serotonin and norepinephrine. The newer Selective Serotonin Re-uptake Inhibitors (SSRIs) have fewer (though still numerous) side effects and fewer interactions with other drugs. 5-HT3 antagonists such as ondansetron, granisetron and tropisetron are important antiemetic agents. They are particularly important in treating the nausea and vomiting which occur during anticancer chemotherapy using cytotoxic drugs. Another application is in treatment of post-operative nausea and vomiting. Applications to the treatment of depression and other mental and psychological conditions have also been investigated with some positive results. Deficient (and sometimes, excessive) intake of various dietary minerals and vitamins can lead to disturbed levels of serotonin via disrupting either the production or reuptake processes. Low serotonin levels are believed to be the cause of many cases of mild to severe depression which can lead to symptoms such as anxiety, apathy, fear, feelings of worthlessness, insomnia and fatigue. The most concrete evidence for the connection between serotonin and depression is the decreased concentrations of serotonin metabolites in the cerebrospinal fluid and brain tissues of depressed people. If depression arises as a result of a serotonin deficiency then pharmaceutical agents that increase the amount of serotonin in the brain should be helpful in treating depressed patients. Anti-depressant medications increase serotonin levels at the synapse by blocking the reuptake of serotonin into the presynaptic cell. Anti-depressants are one of the most highly prescribed medications despite the serious side-effects they can cause. If depression is mild enough it can sometimes be managed without prescribed medications. The most effective way of raising serotonin levels is with vigorous exercise. Studies have shown that serotonin levels are increased with increased activity and the production of serotonin is increased for some days after the activity. This is the safest way of increasing serotonin levels and many other benefits result from regular exercise. Serotonin levels can also be controlled through the diet. A diet deficient in omega-3 fatty acids may lower brain levels of serotonin and cause depression. Complex carbohydrates raise the level of tryptophan in the brain resulting in a calming effect. Vitamin C is also required for the conversion of tryptophan into serotonin. Care must be taken in any attempt to increase serotonin levels, as a dangerous condition known as serotonin syndrome may result. This is especially a concern if multiple serotonergic agents interact to increase 5-HT levels - such as can happen when St Johns Wort is taken in combination with an SSRI. References Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5 ed). Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4
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