thumb|220px|The [[5-HT1B receptor|5-HT<sub>1B</sub> receptor as an example of a metabotropic serotonin receptor. Its crystallographic structure in ribbon representation]]
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 and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin (i.e., 5-hydroxytryptamine, hence "5-HT") receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.
The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, dopamine, epinephrine / norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin, cortisol, corticotropin, and substance P, among others. Serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. The serotonin receptors also affect sexual behaviors and increases in serotonin can cause increases of sexual stimulation. They are the target of a variety of pharmaceutical and recreational drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, psychedelics (hallucinogens), and entactogens. In cases of certain recreational drugs, such as crack cocaine, their use has been shown to negatively impact the response of 5HT receptors in the brain.
Serotonin receptors are found in almost all animals and are even known to regulate longevity and behavioural aging in the primitive nematode, Caenorhabditis elegans.
Classification
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in the central and peripheral nervous systems.
Families
{| class="wikitable"
! Family !! Type !! Mechanism !! Potential
|-
| 5-HT<sub>1</sub> || G<sub>i</sub>/G<sub>o</sub>-protein coupled. || Decreasing cellular levels of cAMP. || Inhibitory
|-
| 5-HT<sub>2</sub> || G<sub>q</sub>/G<sub>11</sub>-protein coupled. || Increasing cellular levels of IP<sub>3</sub> and DAG. || Excitatory
|-
| 5-HT<sub>3</sub> || Ligand-gated Na<sup>+</sup> and K<sup>+</sup> cation channel. || Depolarizing plasma membrane. || Excitatory
|-
| 5-HT<sub>4</sub> || G<sub>s</sub>-protein coupled. || Increasing cellular levels of cAMP. || Excitatory
|-
| 5-HT<sub>5</sub> || G<sub>i</sub>/G<sub>o</sub>-protein coupled. || Decreasing cellular levels of cAMP. || Inhibitory
|-
| 5-HT<sub>6</sub> || G<sub>s</sub>-protein coupled. || Increasing cellular levels of cAMP. || Excitatory
|-
| 5-HT<sub>7</sub> || G<sub>s</sub>-protein coupled. || Increasing cellular levels of cAMP. || Excitatory
|-
|}
Subtypes
The 7 general serotonin receptor classes include a total of 14 known serotonin receptors. The 15th receptor 5-HT<sub>1P</sub> has been distinguished on the basis of functional and radioligand binding studies, its existence has never been definitely affirmed or refuted. The specific types have been characterized as follows:
{| class="wikitable mw-collapsible"
!colspan=13|Information on serotonin receptors (human isoforms if nothing else is stated)
|-
!rowspan=2| Receptor
!rowspan=2| First cloned – PDB entries
!rowspan=2| Gene(s)
!colspan=6| Distribution
!rowspan=2| Function
!rowspan=2| Agonists
!rowspan=2| Antagonists
!rowspan=2| Uses of drugs that act on this receptor
|-
! Blood vessels
! CNS
! GI Tract
! Platelets
! PNS
! Smooth Muscle
|-
| 5-HT<sub>1A</sub>
|1987 –
- 7e2x
- 7e2y
- 7e2z
60px
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- Addiction
- Aggression
- Anxiety
- Appetite
- Autoreceptor
- Blood Pressure
- Cardiovascular Function
- Emesis
- Heart Rate
- Memory
- Mood
- Nausea
- Penile Erection
- Pupil Dilation
- Respiration
- Sexual Behavior
- Sleep
- Sociability
- Thermoregulation
- Vasoconstriction
|<!--5-HT1A AGONISTs-->
<span style="font-size:100%;">Selective (for 5-HT<sub>1A</sub> over other 5-HT receptors) </span>
- Vilazodone (Viibryd)
- F-15,599 (research compound, highly potent and selective for 5-HT<sub>1A</sub>)
- Flesinoxan (potent, EC<sub>50</sub> = 24 nM)
- Gepirone (partial agonist, K<sub>i</sub> = 70 nM)
- Haloperidol
- Ipsapirone (partial agonist, K<sub>i</sub> = 12.1 nM)
- Quetiapine
- Trazodone (SARI, selective in the sense that on all other 5-HT receptors it acts as either an antagonist or has no action. K<sub>d</sub> = 78 nM)
- Yohimbine (unselective partial agonist)
- Tandospirone (potent and selective partial agonist)
<span style="font-size:100%;"> Nonselective </span>
- 5-CT (potent – K<sub>i</sub> = 250 ± 50 pM)
- 8-OH-DPAT (potent)
- Aripiprazole (atypical antipsychotic)
- Asenapine (atypical antipsychotic)
- Buspirone (partial agonist)
- Vortioxetine (high-efficacy partial agonist)
- Ziprasidone (partial agonist, K<sub>i</sub> = 3.4 nM)
- Methylphenidate (weak agonist)
|<!--5-HT1A ANTAGONISTs-->
- BMY 7378
- Cyanopindolol
- Iodocyanopindolol
- Lecozotan
- Methiothepin
- Methysergide
- NAN-190
- Nebivolol
- Nefazodone
- WAY-100,135
- WAY-100,635
- Mefway
|
- Analgesics (agonists)
- Antidepressants (post-synaptic receptor agonists and pre-synaptic autoreceptor antagonists serve as antidepressants)
- Anxiolytics (agonist and antagonist)
|-
| 5-HT<sub>1B</sub>
|1992 –
- 6g79
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- Addiction
- Aggression
- Autoreceptor
- Learning
- Locomotion
- Memory
- Autoreceptor
- Locomotion
|<!--5-HT1P AGONISTs-->
- 5-OHIP
- 2-Methyl-5-HT
- 5-BOHIP
|<!--5-HT1P ANTAGONISTs-->
- 5-HTP-DP
- Anxiety
- Appetite
- Cognition
- Imagination
- Learning
- Memory
- Mood
- Perception
- Sexual Behavior
- Sleep
- Thermoregulation
- Vasoconstriction
|<!--5-HT2A AGONISTs-->
- 25I-NBOMe (Full agonist)
- 2C-B
- 2C-I
- 5-MeO-DMT
- Aripiprazole (very weak partial agonist or antagonist)
- BZP
- Bufotenin
- DMT
- DOM
- Ergonovine
- Lisuride
- LSD
- Mescaline
- PNU-22394 (partial agonist)
- Psilocin
- Psilocybin
- TFMPP (partial agonist or antagonist)
|<!--5-HT2A ANTAGONISTs-->
- Atypical antipsychotics
- Clozapine
- Appetite
- Cardiovascular Function
- GI Motility
- Sleep
- Appetite
- GI Motility
- Heteroreceptor for norepinephrine and dopamine
- Locomotion
- Mood
- Sexual Behavior
- Thermoregulation
- A-372,159
- AL-38022A
- Aripiprazole
- Ergonovine
- Lorcaserin
- PNU-22394 (full agonist)
- Mianserin
- Mirtazapine
- Nefazodone
- Olanzapine
- Paroxetine
- Quetiapine
- Risperidone
- Ritanserin
- SB-242084
- Tramadol
- Trazodone
- Ziprasidone
|
- Antidepressant (antagonists; e.g., agomelatine, fluoxetine, mirtazapine)
- Orexigenic (e.g., mirtazapine, clozapine and olanzapine; antagonists)
- Anorectic (Lorcaserin; agonist)
- Antipsychotic (Vabicaserin; agonists)
|-
| 5-HT<sub>3</sub>
|1993
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- Addiction
- Anxiety
- Emesis
- GI Motility
- Learning
- Memory
- Appetite
- GI Motility
- Learning
- Memory
- Mood
- Respiration
|<!--5-HT4 AGONISTs-->
- 5-MT
- BIMU-8
- Cinitapride
- Cisapride
- Sleep
|<!--5-HT5A AGONISTs-->
- 5-CT
- Ergotamine
- Lisuride (partial)
- Methylergometrine (full)
- Cognition
- Learning
- Memory
|<!--5-HT6 AGONISTs-->
- EMD-386,088
- EMDT
- WAY-181,187
- WAY-208,466
- E-6837
- N-(inden-5-yl)imidazothiazole-5-sulfonamide (43)
|<!--5-HT6 ANTAGONISTs-->
- Amitriptyline
- Aripiprazole
- Asenapine
- Clomipramine
- Clozapine
- Dimebolin
- EGIS-12233
- Haloperidol
- Iloperidone
- MS-245
- Olanzapine
- Ro04-6790
- SB-258,585
- SB-271,046
- SB-357,134
- SB-399,885
|
- Antidepressant (antagonists and agonists)
- Anxiolytic (antagonists and agonist)
- Nootropic (antagonists)
- Anorectic (antagonists)
|-
| 5-HT<sub>7</sub>
|1993
|
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- Anxiety
- Autoreceptor
- Memory
- Mood
- Sleep
- Thermoregulation
- Vasoconstriction
- Immunostimulation
|<!--5-HT7 AGONISTs-->
- 5-CT
- 8-OH-DPAT
- Aripiprazole (partial agonist)
- AS-19
- E-55888
|<!--5-HT7 ANTAGONISTs-->
- Amitriptyline
- Asenapine
- Clomipramine
- Clozapine
- EGIS-12233
- Haloperidol
- Iloperidone
- Imipramine
- Ketanserin
- Mirtazapine
- Olanzapine
- RA-7
- Ritanserin
- Risperidone
- SB-269,970
- Vortioxetine (K<sub>i</sub> = 19 nM)
Very nonselective agonists of 5-HT receptor subtypes include ergotamine (an antimigraine), which activates 5-HT<sub>1A</sub>, 5-HT<sub>1D</sub>, 5-HT<sub>1B</sub>, D<sub>2</sub> and norepinephrine receptors.
5-HT-like
A number of receptors were classed as "5-HT-like" - by 1998 it was being argued that, since these receptors were "a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7" receptors the classification was redundant.