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Serotonin The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems.[1][2] They mediate both excitatory and inhibitory neurotransmission. The serotonin 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. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and illicit drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.[3]
Classification
With the exception of the 5-HT3 receptor, a ligand-gated ion channel, all other serotonin receptors are G protein-coupled receptors that activate an intracellular second messenger cascade to produce an excitatory or inhibitory response.
Families
Family Type 5-HT1 Gi/Go-protein coupled. 5-HT2 Gq/G11-protein coupled. Ligand-gated Na+ and K+ cation channel. 5-HT4 Gs-protein coupled. 5-HT3 Mechanism Decreasing cellular levels of cAMP. Increasing cellular levels of IP3 and DAG. Depolarizing plasma membrane. Increasing cellular levels of cAMP. Potential Inhibitory Excitatory Excitatory Excitatory
Decreasing cellular levels of cAMP. Increasing cellular levels of cAMP. Increasing cellular levels of cAMP.
[edit] Subtypes
Within these general classes of serotonin receptors, a number of specific types have been characterized:[5][6][7] Overview of Serotonin Receptors Rece Distribu Gene(s) Function ptor tion Addiction
[8][9][10]
Agonists
Antagonists
Blood Pressure[14]
[15]
5HT1A
HTR 1A
B lo o d V es se ls C N S
Mood[21] Nausea[17] Nociceptio n[22] Penile Erection[23] Pupil Dilation[24] Respiratio n[25] Sexual Behavior[2
Cannabidiol Clozapine Dihydroergota mine Eltoprazine Ergotamine Flesinoxan Flibanserin Gepirone Ipsapirone Methysergide Nefazodone Psilocin Quetiapine RU 24969 Tandospirone Trazodone Urapidil Xaliproden Yohimbine Ziprasidone
Alprenolol Asenapine BMY 7378 Cyanopindolol Iodocyanopindol ol Lecozotan Methiothepin NAN-190 Nebivolol Oxprenolol Pindolol Propanolol Robalzotan S15535 Spiperone TFMPP UH-301 WAY-100,135 WAY-100,635 Mefway
6]
Sleep[27] Sociability
[28]
5HT1B
HTR 1B
B lo o d V es se ls C N S
Learning[36
]
Vasoconstr iction
5-CT CP-93,129 CP-94,253 Dihydroergota mine Eltoprazine Ergotamine Methysergide RU 24969 TFMPP Triptans[31] (antimigraine[3 1] ) o Zolmitr iptan o Eletript an o Sumatr iptan 5-CT Dihydroergota mine Ergotamine Methysergide Triptans[31] (antimigraine[3 1] ) o Almotr iptan o Eletript an o Frovatr iptan o Naratri ptan
Alprenolol AR-A000002 Asenapine Cyanopindolol GR 127935 Iodocyanopindol ol Isamoltane Metergoline Methiothepin Oxprenolol Pindolol Propanolol SB-216,641 Yohimbine
5HT1D
HTR 1D
B lo o d V es se ls C N S
Anxiety[38]
[39]
HTR 1E
B lo o d V es se ls C N S C N S B lo o d V es se ls C N S G I T ra ct Pl at el et s P
Methiothepin
5HT1F
HTR 1F
Migraine
LY334370 COL-144
5HT2A
HTR 2A
Addiction (potentiall y modulatin g) [40] Anxiety[41] Appetite Cognition Imaginatio n Learning Memory Mood Perception Sexual Behavior[4
2]
2C-B 5-MeO-DMT BZP Bufotenin DMT DOM Ergonovine Lisuride LSD Mescaline Myristicin Psilocin Psilocybin TFMPP (partial agonist or antagonist) Yohimbine
Atypical antipsychotics o Clozapin e[31] o Olanzapi ne o Quetiapi ne o Risperid one o Ziprasid one Aripiprazole Asenapine Amitriptyline Clomipramine Cyproheptadine Eplivanserin Etoperidone Iloperidone Ketanserin[31] (antihypertensiv
N S S m o ot h M u sc le B lo o d V es se ls C N S G I T ra ct Pl at el et s P N S S m o ot h M u sc le
iction[45]
Anxiety[46]
[47][48]
Appetite[49
]
5HT2B
HTR 2B
5HT2C
HTR 2C
B lo o d V es se ls C N S G I T ra ct Pl at el et s P N S S m o ot h M u sc le C N S G I T ra ct P N S
Penile Erection[55]
[56]
Sexual Behavior[4
2]
A-372,159 AL-38022A Aripiprazole Ergonovine Lorcaserin Ro60-0175 TFMPP Trazodone[31] (hypnotic[31]) YM-348
Agomelatine[31] (antidepressant[3 1] ) Amitriptyline Asenapine Clomipramine Clozapine[31] (antipsychotic[31] ) Cyproheptadine Dimebolin Eltoprazine Etoperidone Fluoxetine Iloperidone Ketanserin[31] (antihypertensiv e[31]) Lisuride Methysergide[58] Mianserin Mirtazapine Nefazodone Olanzapine Quetiapine Risperidone Ritanserin Trazodone Ziprasidone
5HT3
Memory[59
]
Nausea
Anxiety[60]
[61]
5HT4
HTR 4
C N S G I T ra ct P N S
Appetite[62
][63]
GI Motility Learning[64
][65]
Memory[64
][65][66]
Mood
]
[67][68
Respiratio n[25][69]
5-MT BIMU-8 Cinitapride Cisapride[31] (gastroprokine tic) Dazopride Metocloprami de Mosapride Prucalopride RS-67333 Renzapride Tegaserod Zacopride
L-Lysine[60] Piboserod
5HT5A
HTR 5A
C N S
Asenapine Dimebolin Methiothepin Ritanserin SB-699,551 SB-699,551-A Amitriptyline Aripiprazole Asenapine Clomipramine Clozapine Dimebolin EGIS-12233 Iloperidone MS-245 Olanzapine Ro04-6790 SB-258,585 SB-271,046[77] SB-357,134 SB-399,885
Anxiety[72]
[73]
Cognition[
74]
5HT6
HTR 6
C N S
Learning[75
]
EMD-386,088 EMDT
Memory[75
]
Mood[73][76
]
5HT7
HTR 7
B lo o d V es se ls C N S G I T ra ct
Anxiety[78]
[79]
Memory[80
][81]
Mood[78][79
]
Amitriptyline Aripiprazole Asenapine Clomipramine Clozapine EGIS-12233 Iloperidone Imipramine Ketanserin Mirtazapine Olanzapine Ritanserin Risperidone SB-269,970
Note that there is no 5-HT1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT2 family of receptors and was redesignated as the 5-HT2C receptor. Note that there is also no 5-HT5B receptor, as it exists only in mice and rats and not in humans or monkeys. Very nonselective agonists of 5-HT receptor subtypes include ergotamine (an antimigraine), which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.[31] LSD (a psychedelic) is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist.[3