Serotonin antagonists are drugs that block serotonin receptors, thereby attenuating or completely abolishing the effects of serotonin. Depending on receptor affinity, individual serotonin antagonists have different effects.
What is a serotonin antagonist?
Serotonin antagonists are drugs that block serotonin receptors, weakening or completely reversing the effects of serotonin. Due to their chemical properties, serotonin antagonists can bind to cell receptors that are actually intended for the neurotransmitter or hormone serotonin. Serotonin antagonists are also known as serotonin agonists. The individual agonists react selectively. They bind only to certain receptors. Since 14 types of serotonin receptors are distinguished, there are also just as many groups of serotonin antagonists. The effect varies from group to group. For example, the drugs are used to treat migraine or anxiety disorders. Some serotonin antagonists also belong to the group of antiemetics. These are effective against nausea and vomiting. Other representatives of the agonists have psychedelic effects and are abused as smoking drugs.
Pharmacologic action
Serotonin antagonists can bind to serotonin receptors in the body. Through the serotonin receptors, the tissue hormone serotonin mediates its physiological and also its pathological effects. Serotonin is found in the nervous system of the intestine, in the cardiovascular system, in the blood and in the central nervous system, among others. The substance has many different effects in the body. It provides both contraction and relaxation of the smooth muscle of blood vessel walls, it affects blood clotting, and it performs various sensory and motor functions in the gastrointestinal tract. Like serotonin itself, its receptors are predominantly found in the central nervous system, cardiovascular system, blood and gastrointestinal tract. There are 14 different types of serotonin receptors in the human body. These are grouped into 7 groups and referred to as 5-HT1 to 5-HT7 receptors. Depending on their chemical structure, serotonin antagonists bind to one or the other group of receptors. By binding, they block the receptor so that serotonin can no longer dock to this receptor. This inhibits the action of serotonin.
Medical application and use
5-HT3 receptor antagonists such as dolasetron, ondansetron, or tropisetron block the vomiting center. The 5-HT3 receptors are found exclusively on central and peripheral neurons. Among other things, they are responsible for triggering the vomiting reflex. Serotonin antagonists from this group of drugs are used to treat cytostatic-induced vomiting. Nausea and vomiting are among the most common side effects of chemotherapy with cytostatic drugs. However, if nausea and vomiting are due to irritation of the vagus nerve, administration of opioids or inner ear disorders, serotonin antagonists have little effect. 5-HT2 antagonists are used in the treatment of depression. Typical drugs from this group are pizotifen, ketanserin or trazodone. Methysergide also belongs to the group of 5-HT2 antagonists. The drug is no longer approved due to severe side effects. The inhibition of 5HT2a receptors has an anxiolytic effect. These drugs also block the presynaptic 5-HT1 autoreceptors. This in turn results in increased release of serotonin into the synaptic cleft. A deficiency of serotonin in the synaptic cleft is manifested by a lack of drive and depressed mood. Indications for 5-HT2 antagonists are therefore depression, obsessive-compulsive disorder, panic attacks, post-traumatic stress disorder (PTSD), and borderline syndromes. 5-HT1 serotonin antagonists are used in migraine therapy. These serotonin antagonists include various triptans such as sumatriptan, rizatriptan, or naratriptan. By blocking receptors, the drugs cause a reduced release of inflammatory peptides. At the same time, they prevent vasoconstriction of blood vessels in the brain. Serotonin antagonists of the 5-HT1 group are also used in the treatment of ADHD. Methylphenidates such as Ritalin are subject to narcotic regulations. Various psychedelic agents such as psilocybin, ergin or mescaline block the 5-HT2 receptors.
Risks and side effects
The side effects of each serotonin antagonist can vary widely. There are drugs that are very well tolerated. Other drugs cause such severe side effects that they had to be withdrawn from the market. Typical adverse drug reactions include headache, fatigue, and dizziness. Gastrointestinal tract disorders are frequently observed. These include diarrhea and constipation. Some of the patients also complain of insomnia. Flu-like symptoms may also occur. Prolonged use may increase liver enzymes in the blood. Some serotonin antagonists result in severe dullness. Patients feel tired and sleepy. Feelings can only be perceived in a muted way. In some cases, sufferers have an increased appetite. Other possible side effects of serotonin antagonists include visual disturbances, urinary retention, dry mucous membranes, cardiac arrhythmias or dizziness. Serotonin antagonists must not be used in cases of known disorders of intestinal activity. Other contraindications include known hypersensitivity to the drugs and pregnancy.
