Serotonin receptors

Serotonin receptors, also known as 5-hydroxytryptamine, or 5-HT receptors, are a family of

guanine nucleotide triphosphate-binding protein-coupled receptors and one ligand-gated ion
channel that convert an extracellular signal from the neurotransmitter 5-HT to an intracellular
reaction. Numerous physiological processes are impacted by these receptors. Since 5-HT
receptors influence a wide range of neuronal, physiological, and behavioral processes, it is not
surprising that 5-HT receptor dysfunction and regulation are linked to a wide range of disorders
and disease states. Therefore, knowledge of the multitudinous coupling pathways, their effector
linkage, and the regulation of these pathways is essential to the etiology of disease and the
development of new therapeutic targets.

1- Classification
Based on their pharmacological characteristics, structure, and function, serotonin receptors—also
referred to as 5-HT receptors or 5-hydroxytryptamine receptors—are divided into several
subtypes. These receptors are essential for mediating the effects of serotonin, a neurotransmitter
that is involved in many different physiological and neurological functions.
Serotonin Receptor Classification:
1. 5-HT1 Family: This group of receptors consists of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E,
and 5-HT1F. These belong to the superfamily of G protein-coupled receptors.
Neurotransmitter release, mood, anxiety, appetite, sleep patterns, and thermoregulation
are all influenced by these receptors.
2. 5-HT2 Family: The 5-HT2A, 5-HT2B, and 5-HT2C receptors comprise the 5-HT2 family.
These receptors, which are widely dispersed throughout the central and peripheral
nervous systems, are also G protein-coupled receptors. Numerous processes, including
mood, perception, learning, memory, sexual behavior, and vasoconstriction, are
influenced by them.
3. 5-HT3 Receptor: Unlike other serotonin receptors, the 5-HT3 receptor is a ligand-gated
ion channel as opposed to a G protein-coupled receptor. It is present in both the peripheral
and central nervous systems and is involved in neurotransmission. Addiction, anxiety,
 emesis (vomiting), GI motility, learning, memory, and nausea can all be impacted by 5-
HT3 receptor activation.
4. Other Receptors: Other serotonin receptors, such as the 5-HT4, 5-HT5A, 5-HT5B, 5-HT6,
and 5-HT7 receptors, have been identified in addition to the families mentioned above.
These receptors are involved in a number of physiological processes and serve a variety
of purposes.

2- Mechanism of action
There are numerous serotonin receptors, and each one functions differently. For every serotonin
receptor, there are two different mechanisms of action:
1. 5-HT1A Receptor:
▪ Increased intracellular cyclic adenosine monophosphate (cAMP) levels are caused by the
5-HT1A receptor's inhibition of adenylate cyclase activity. In the end, this leads to a
decrease in the release of neurotransmitters and an inhibition of neuronal activity.
2. 5-HT2A Receptor:
▪ Phospholipase C (PLC) pathway stimulation by the 5-HT2A receptor results in the
synthesis of diacylglycerol (DAG) and inositol trisphosphate (IP3). Calcium is released
from intracellular reserves by IP3, and protein kinase C (PKC) is activated by DAG. The
excitability of neurons and synaptic transmission are regulated by these signaling
cascades.
3. 5-HT3 Receptor:
▪ Other neurotransmitters, like dopamine and gamma-aminobutyric acid (GABA), are also
released from presynaptic terminals in response to activation of the 5-HT3 receptor.

3- Function
1. 5-HT1 Receptors:
▪ 5-HT1 receptors is the inhibition of adenylyl cyclase, which lowers the amount of cyclic
adenosine monophosphate (cAMP) produced when 5-HT1 receptors are activated.
2. 5-HT2 Receptors:
▪ Modulation of Cognition and Mood: 5-HT2 receptors are involved in cognitive functions
like memory and learning as well as mood regulation.
 3. 5-HT3 Receptors:
▪ 5-HT3 receptors are ligand-gated ion channels, in contrast to other serotonin receptors.
Neuronal depolarization results from the activation of these receptors, which permits the

influx of cations like calcium and sodium.

Serotonin Receptors Agonists Antagonists

5-HT1 Receptors Sumatriptan,Naratriptan
Rizatriptan ,Eletriptan
5-HT2 Receptors Lysergic acid diethylamide (LSD)
Psilocybin, Mescaline, DOI (2,5-
Dimethoxy-4-iodoamphetamine)
5-HT3 Receptors 2-Methyl-5-HT, Phenylbiguanide,
M-Chlorophenylbiguanide
4- Agonists/Antagonists
Pindolol, Methiothepin
GR127935, SB-224289
Ketanserin, Risperidone,
Olanzapine, Quetiapine
Zacopride, MDL72222,
Tropisetron, Ondansetron,
Granisetron

Serotonin is much more than just a neurotransmitter that is necessary for mood regulation, as
these examples demonstrate. It controls many different physiological and pathological processes
in the majority of human organs. This elucidates why serotonergic drugs, in addition to their
widely acknowledged impacts on mood and cognition, also regulate phenomena ranging from
ejaculatory latency to hemostatic function.
Through several, frequently conflicting mechanisms, serotonin typically regulates a given
physiological process (such as energy balance, pain perception, or digestion) at multiple steps.
Serotonin, for instance, modifies nociceptive processing at different levels of the nervous system,
thereby acting as a potent pro- and anti-analgesic.
 Reference:
▪ https://pubmed.ncbi.nlm.nih.gov/2446065/
▪ https://www.ncbi.nlm.nih.gov/books/NBK545168/
▪ https://www.sciencedirect.com/topics/neuroscience/5-ht-receptor
▪ https://www.drugs.com/drug-class/5ht3-receptor-antagonists.html