QUESTIONS & ANSWERS: GLOSSARY
Serotonin (5HT) and 5HT2 antagonism
5-hydroxytryptamine (5HT) is a body chemical found almost entirely within the brain and the platelets; some serotonin is also released into blood from cells in the gut, tumours of which can cause a disease called carcinoid syndrome. In the brain and nervous system, it carries messages from one neurone to another (a "neurotransmitter").
Serotonin is released in high concentration from activated platelets and then activates more platelets via their 5HT2 receptors. This is called a "snowball effect" or "positive feedback". Fortunately, the important receptors in the nervous system are not of the 5HT2 subtype, so that treatment with 5HT2 antagonists does not cause detectable changes in cerebral performance. These antagonists have been shown to stop platelet-rich coronary thrombosis without causing bleeding and are therefore of particular interest to the Coronary Thrombosis Trust as a potential future treatment for coronary heart disease.
Serotonin acts on endothelium so that the cells release nitric oxide and the blood vessel relaxes (gets wider, also known as vasodilatation). With damaged vessels, as in coronary thrombosis, the serotonin acts directly on the arterial wall muscle, causing it to narrow (vasoconstriction) and making obstruction to blood flow in the coronary artery. This evil consequence of coronary thrombosis would also be reversed by 5HT2 antagonism.
5HT2 antagonism is one way to influence the platelet serotonin system. Another is to block uptake of serotonin into the platelets. This happens when a class of drug called serotonin re-uptake inhibitors is given to treat patients with depression. In this case, the drug prevents the platelets having so much serotonin within them, less is released upon activation. These patients are protected against coronary thrombosis, without bleeding, after about 6 weeks of treatment. This is too long for them to be useful once a coronary thrombosis has occurred; for this we need a serotonin 5HT2 receptor antagonist.
When a clot from a vein lodges in the lungs to cause obstruction of blood flow (pulmonary embolism), serotonin released from the platelets causes the blood vessels in the lungs to constrict, making the obstruction to blood flow worse. It is likely that 5HT2 antagonism would ameliorate this problem, but clinical trials have not been performed. Although there is no commercial funding for this research, the University of Aberdeen have obtained one of these antagonists which is out of patent - called thromboserin-noble. An additional £42,000 is required to get this tested. Please help us with this essential research by making a donation.