5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''HTR5A''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Agonists
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...
and
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.5-hydroxytryptamine receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...
s, negatively influencing cAMP levels via Gi and Go. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. The 5-HT5A receptor has been shown to be functional in a native expression system.
Rodents have been shown to possess two functional 5-HT5 receptor subtypes, 5-HT5A and 5-HT5B, however while humans possess a gene coding for the 5-HT5B subtype, its coding sequence is interrupted by stop codons, making the gene non-functional, and so only the 5-HT5A subtype is expressed in human brain.
It also appears to serve as a presynaptic serotonin autoreceptor.
Clinical significance
The neurotransmitter
serotonin
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
(5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects.
Selective ligands
Few highly selective ligands are commercially available for the 5-HT5A receptor, though the field has expanded considerably in recent years. When selective activation of this receptor is desired in scientific research, the non-selective serotonin receptor agonist 5-Carboxamidotryptamine can be used in conjunction with selective antagonists for its other targets (principally 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT7). Research in this area is ongoing.
Lisuride
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline family which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
Side effects of l ...
Methylergometrine
Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and as an antimigraine agent in the treatment of mi ...
full agonist.
* Valerenic acid a component of valerian, has been shown to act as a 5HT5A partial agonist.
*
Olanzapine
Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomitin ...
an
atypical antipsychotic
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...
.
*Psilocin
*
Aripiprazole
Aripiprazole, sold under the brand name Abilify, among others, is an atypical antipsychotic primarily used in the treatment of schizophrenia, bipolar disorder, and irritability associated with autism spectrum disorder; other uses include as ...
- an atypical antipsychotic
*
Mirtazapine
Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...
- an
atypical antidepressant
An atypical antidepressant is any antidepressant medication that acts in a manner that is different from that of most other antidepressants.
Atypical antidepressants include:
* agomelatine
* bupropion
* iprindole
* opipramol
* tianeptine
* ...
* UCSF648 - selective 5-HT5A partial agonist
* Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT5A agonist with Ki = 124 nM.
Antagonists
*
ASP5736
ASP5736 is an experimental drug developed by Astellas Pharma, which acts as a selective antagonist for the serotonin receptor 5-HT5A, with significantly higher potency than the older drug SB-699,551. In animal studies, it was found to reduce dr ...
Latrepirdine
Latrepirdine ( INN, also known as dimebolin and sold as Dimebon) is an antihistamine drug which has been used clinically in Russia since 1983.
Research was conducted in both Russia and western nations into potential applications as a neuroprotec ...
(non-selective).
*
Risperidone
Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...
(non-selective), moderate 206 nM affinity.
*
SB-699,551
SB-699551 is a drug which was the first compound developed to act as a selective antagonist for the serotonin receptor 5-HT5A, with selectivity of around 100x over other serotonin receptor subtypes. Multiple therapeutic roles have been suggested ...
See also
*
5-HT receptor
5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the Central nervous system, central and peripheral nervous systems ...