5-HT receptor

From Wikipedia, the free encyclopedia
The 5-HT1B 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 the central and peripheral nervous systems.[1][2][3] 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. Serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. They are the target of a variety of pharmaceutical and recreational drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.[4]

Serotonin receptors are found in almost all animals and are even known to regulate longevity and behavioral aging in the primitive nematode, Caenorhabditis elegans.[5][6]

Classification[]

5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in the central and peripheral nervous systems.[1][2] They can be divided into 7 families of G protein-coupled receptors except for the 5-HT3 receptor, a ligand-gated ion channel, which activates an intracellular second messenger cascade to produce an excitatory or inhibitory response. In 2014, a novel 5-HT receptor was isolated from the small white butterfly, Pieris rapae, and named pr5-HT8. It does not occur in mammals and shares relatively low similarity to the known 5-HT receptor classes.[7]

Families[]

Family Type Mechanism Potential
5-HT1 Gi/Go-protein coupled. Decreasing cellular levels of cAMP. Inhibitory
5-HT2 Gq/G11-protein coupled. Increasing cellular levels of IP3 and DAG. Excitatory
5-HT3 Ligand-gated Na+ and K+ cation channel. Depolarizing plasma membrane. Excitatory
5-HT4 Gs-protein coupled. Increasing cellular levels of cAMP. Excitatory
5-HT5 Gi/Go-protein coupled.[8] Decreasing cellular levels of cAMP. Inhibitory
5-HT6 Gs-protein coupled. Increasing cellular levels of cAMP. Excitatory
5-HT7 Gs-protein coupled. Increasing cellular levels of cAMP. Excitatory

Subtypes[]

The 7 general serotonin receptor classes include a total of 14 known serotonin receptors.[9] The specific types have been characterized as follows:[10][11][12]

Overview of serotonin receptors
Receptor First cloned Gene(s) Distribution Function Agonists Antagonists Uses of drugs that act on this receptor
Blood vessels CNS GI Tract Platelets PNS Smooth Muscle
5-HT1A 1987 Yes Yes No No No No

Selective (for 5-HT1A over other 5-HT receptors)

  • Vilazodone (Viibryd)
  • F-15,599 (research compound, highly potent and selective for 5-HT1A)
  • Flesinoxan (potent, EC50 = 24 nM)
  • Gepirone (partial agonist, Ki = 70 nM)
  • Haloperidol
  • Ipsapirone (partial agonist, Ki = 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. Kd = 78nM)
  • Yohimbine (unselective partial agonist)
  • Tandospirone (potent and selective partial agonist)

Nonselective

  • 5-CT (potent - Ki = 250±50 pM)
  • 8-OH-DPAT (potent)
  • Aripiprazole (atypical antipsychotic)
  • Asenapine (atypical antipsychotic)
  • Buspirone[36] (partial agonist)
  • Vortioxetine (high-efficacy partial agonist)[37]
  • Ziprasidone (Partial agonist, Ki = 3.4 nM)
  • Methylphenidate (weak agonist)
  • BMY 7378
  • Cyanopindolol
  • Iodocyanopindolol
  • Lecozotan
  • Methiothepin
  • Methysergide[38]
  • 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[39] (antagonist)
5-HT1B 1992 Yes Yes No No No No
  • 5-CT
  • CGS-12066A
  • CP-93,129
  • CP-94,253
  • Dihydroergotamine
  • Eltoprazine
  • Ergotamine
  • Methysergide
  • RU 24969
  • TFMPP
  • Triptans[36] (antimigraine[36])
    • Zolmitriptan
    • Eletriptan
    • Sumatriptan
  • Vortioxetine (partial agonist, Ki = 33 nM)[37]
  • Alprenolol
  • AR-A000002
  • Asenapine
  • Cyanopindolol
  • GR-127,935
  • Iodocyanopindolol
  • Isamoltane
  • Metergoline
  • Methiothepin
  • Oxprenolol
  • Pindolol
  • Propranolol
  • SB-216,641
  • Yohimbine
  • Migraines (e.g. triptans)
5-HT1D 1991 Yes Yes No No No No
  • Anxiety[46][47]
  • Autoreceptor
  • Locomotion[45]
  • Vasoconstriction
  • 5-CT
  • CP-135,807
  • Dihydroergotamine
  • Ergotamine
  • Methysergide
  • Triptans[36] (antimigraine[36])
    • Almotriptan
    • Eletriptan
    • Frovatriptan
    • Naratriptan
    • Rizatriptan
    • Sumatriptan
    • Zolmitriptan
  • Yohimbine
  • BRL-15572
  • GR-127,935
  • Ketanserin
  • Metergoline
  • Methiothepin
  • Rauwolscine
  • Ritanserin
  • Vortioxetine (Ki = 54 nM)[37]
  • Ziprasidone
  • Migraines (e.g. triptans)
5-HT1E 1992 Yes Yes No No No No
  • None known
5-HT1F 1993 No Yes No No No No
  • Migraine
  • BRL-54443
  • Lasmiditan
  • LY-334,370
  • Naratriptan
  • Eletriptan
  • None known
5-HT2A 1988 Yes Yes Yes Yes Yes Yes
  • Addiction (potentially modulating) [48]
  • Anxiety[49]
  • Appetite
  • Cognition
  • Imagination
  • Learning
  • Memory
  • Mood
  • Perception
  • Sexual Behavior[50]
  • Sleep[51]
  • Thermoregulation[52]
  • Vasoconstriction[53]
  • 25I-NBOMe (Full agonist)
  • 5-MeO-DMT
  • BZP
  • Bufotenin
  • DMT
  • DOM
  • Ergonovine
  • Lisuride
  • LSD
  • Mescaline
  • PNU-22394 (Partial agonist)[54][55][56]
  • Psilocin
  • Psilocybin
  • TFMPP (partial agonist or antagonist)
  • Atypical antipsychotics
  • Aripiprazole
  • Asenapine
  • Amitriptyline
  • Clomipramine
  • Cyproheptadine
  • Doxepin
  • Eplivanserin
  • Etoperidone
  • Haloperidol
  • Hydroxyzine
  • Iloperidone
  • Ketanserin[36] (antihypertensive[36])
  • Methysergide
  • Mianserin
  • Mirtazapine
  • Nefazodone
  • Pimavanserin
  • Pizotifen
  • Ritanserin
  • Trazodone
  • Yohimbine
  • Atypical antipsychotics (antagonist)
  • Psychedelics (agonists)
  • NaSSAs (antidepressants and anxiolytics; they serve as antagonists at this site)
  • Treating serotonin syndrome (antagonists; e.g. cyproheptadine)
  • Sleeping aid (antagonists; e.g. trazodone)
5-HT2B 1992 Yes Yes Yes Yes Yes Yes
  • 6-APB (full agonist)
  • BW-723C86
  • Fenfluramine
  • MDMA
  • Norfenfluramine
  • PNU-22394 (Partial agonist)[54][55][56]
  • Ro60-0175
  • Methylphenidate (weak agonist)
  • Migraines (antagonists)
5-HT2C 1988 Yes Yes Yes Yes Yes Yes
  • Addiction. (potentially modulating)[48]
  • Anxiety[62][63][64]
  • Appetite
  • GI Motility[65]
  • Heteroreceptor for norepinephrine and dopamine
  • Locomotion
  • Mood[63][64]
  • Penile Erection[66][67]
  • Sexual Behavior[50]
  • Sleep[68]
  • Thermoregulation[52]
  • Vasoconstriction
  • Antidepressant (antagonists; e.g. agomelatine, fluoxetine, mirtazapine)
  • Orexigenic (e.g. mirtazapine, clozapine and olanzapine; antagonists)
  • Anorectic (Lorcaserin; agonist)
  • Antipsychotic (Vabicaserin; agonists)
5-HT3 1993 No Yes Yes No Yes No
  • Addiction
  • Anxiety
  • Emesis
  • GI Motility[71]
  • Learning[72]
  • Memory[72]
  • Nausea
  • Alosetron
  • Several antiemetics[36]
    • Dolasetron
    • Ondansetron[36]
    • Granisetron
    • Tropisetron
  • Clozapine
  • Memantine
  • Metoclopramide
  • Mianserin
  • Mirtazapine
  • Olanzapine
  • Quetiapine
  • Vortioxetine (Ki = 3.7 nM)[37]
  • Antiemetic
  • Antidepressant (e.g. mirtazpine)
  • antipsychotic (e.g. olanzapine, quetiapine)
5-HT4 1995 No Yes Yes No Yes No
  • L-Lysine[73]
  • Piboserod
  • Gastroprokinetics (e.g. Tegaserod)
5-HT5A 1994 No Yes No No No No
  • 5-CT
  • Ergotamine
  • Valerenic Acid (partial agonist)[84]
  • Asenapine
  • Dimebolin
  • Methiothepin
  • Ritanserin
  • SB-699,551
  • SB-699,551-A
  • None thus far
5-HT5B 1993 No No No No No No

Functions in rodents,
pseudogene in humans

  • None thus far
5-HT6 1993 No Yes No No No No
  • EMD-386,088
  • EMDT
  • Amitriptyline
  • Aripiprazole
  • Asenapine
  • Clomipramine
  • Clozapine
  • Dimebolin
  • EGIS-12233
  • Haloperidol
  • Iloperidone
  • MS-245
  • Olanzapine
  • Ro04-6790
  • SB-258,585
  • SB-271,046[90]
  • SB-357,134
  • SB-399,885
  • Antidepressant (antagonists and agonists)
  • Anxiolytic (antagonists and agonist)
  • Nootropic (antagonists)
  • Anorectic (antagonists)
5-HT7 1993 Yes Yes Yes No No No
  • Amitriptyline
  • Asenapine
  • Clomipramine
  • Clozapine
  • EGIS-12233
  • Haloperidol
  • Iloperidone
  • Imipramine
  • Ketanserin
  • Mirtazapine
  • Olanzapine
  • Ritanserin
  • Risperidone
  • SB-269,970
  • Vortioxetine (Ki = 19 nM)[37]
  • Antidepressant (antagonists)
  • Anxiolytics (antagonists)
  • Nootropic (antagonists)

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.[98]

Very nonselective agonists of 5-HT receptor subtypes include ergotamine (an antimigraine), which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.[36] LSD (a psychedelic) is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A and 5-HT6 agonist.[36]

Expression patterns[]

The genes coding for serotonin receptors are expressed across the mammalian brain. Genes coding for different receptors types follow different developmental curves. Specifically, there is a developmental increase of HTR5A expression in several subregions of the human cortex, paralleled by a decreased expression of HTR1A from the embryonic period to the post-natal one. [99]

5-HT1-like[]

A number of receptors were classed as "5-HT1-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.[100]

References[]

  1. ^ a b Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994). "International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)". Pharmacol. Rev. 46 (2): 157–203. PMID 7938165.
  2. ^ a b Frazer A, Hensler JG (1999). "Chapter 13: Serotonin Receptors". In Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (eds.). Basic Neurochemistry: MolecularCellular, and Medical Aspects. Philadelphia: Lippincott-Raven. pp. 263–292. ISBN 978-0-397-51820-3.
  3. ^ Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M.; Svarer, Claus; Greve, Douglas N.; Knudsen, Gitte M. (2017-01-04). "A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System". Journal of Neuroscience. 37 (1): 120–128. doi:10.1523/jneurosci.2830-16.2016. PMC 5214625. PMID 28053035.
  4. ^ Nichols DE, Nichols CD (May 2008). "Serotonin receptors". Chem. Rev. 108 (5): 1614–41. doi:10.1021/cr078224o. PMID 18476671.
  5. ^ Murakami H, Murakami S (August 2007). "Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity". Aging Cell. 6 (4): 483–8. doi:10.1111/j.1474-9726.2007.00303.x. PMID 17559503. S2CID 8345654.
  6. ^ Murakami H, Bessinger K, Hellmann J, Murakami S (July 2008). "Manipulation of serotonin signal suppresses early phase of behavioral aging in Cnorhabditis elegans". Neurobiology of Aging. 29 (7): 1093–100. doi:10.1016/j.neurobiolaging.2007.01.013. PMID 17336425. S2CID 37671716.
  7. ^ Qi YX, Xia RY, Wu YS, Stanley D, Huang J, Ye GY (2014). "Larvae of the small white butterfly, Pieris rapae, express a novel serotonin receptor". J. Neurochem. 131 (6): 767–77. doi:10.1111/jnc.12940. PMID 25187179. S2CID 21621635.
  8. ^ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (1998). "The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells". Eur J Pharmacol. 361 (2–3): 299–309. doi:10.1016/S0014-2999(98)00744-4. PMID 9865521.
  9. ^ Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 4. ISBN 9780071481274. Similarly, little is known about which of serotonin's 14 known receptors must be activated to achieve an antidepressant response.
  10. ^ Glennon RA, Dukat M, Westkaemper RB (2000-01-01). "Serotonin Receptor Subtypes and Ligands". American College of Neurophyscopharmacology. Archived from the original on 21 April 2008. Retrieved 2008-04-11.
  11. ^ "5-Hydroxytryptamine Receptors". IUPHAR Receptor Database. International Union of Basic and Clinical Pharmacology. Retrieved 2008-04-11.
  12. ^ Wesolowska A (2002). "In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors" (PDF). Polish Journal of Pharmacology. 54 (4): 327–41. PMID 12523486.
  13. ^ Tomkins DM, Higgins GA, Sellers EM (1994). "Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake". Psychopharmacology. 115 (1–2): 173–9. doi:10.1007/BF02244769. PMID 7862892. S2CID 38012716.
  14. ^ Müller CP, Carey RJ, Huston JP, De Souza Silva MA (2007). "Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors". Prog. Neurobiol. 81 (3): 133–78. doi:10.1016/j.pneurobio.2007.01.001. PMID 17316955. S2CID 42788995.
  15. ^ Carey RJ, DePalma G, Damianopoulos E, Shanahan A, Müller CP, Huston JP (2005). "Evidence that the 5-HT1A autoreceptor is an important pharmacological target for the modulation of cocaine behavioral stimulant effects". Brain Res. 1034 (1–2): 162–71. doi:10.1016/j.brainres.2004.12.012. PMID 15713268. S2CID 28356741.
  16. ^ a b de Boer SF, Koolhaas JM (2005). "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". Eur J Pharmacol. 526 (1–3): 125–39. doi:10.1016/j.ejphar.2005.09.065. PMID 16310183.
  17. ^ Parks CL, Robinson PS, Sibille E, Shenk T, Toth M (1998). "Increased anxiety of mice lacking the serotonin1A receptor". Proceedings of the National Academy of Sciences of the United States of America. 95 (18): 10734–9. Bibcode:1998PNAS...9510734P. doi:10.1073/pnas.95.18.10734. PMC 27964. PMID 9724773.
  18. ^ Ebenezer IS, Arkle MJ, Tite RM (1998). "8-Hydroxy-2-(di-n-propylamino)-tetralin inhibits food intake in fasted rats by an action at 5-HT1A receptors". Methods Find Exp Clin Pharmacol. 29 (4): 269–72. doi:10.1358/mf.2007.29.4.1075362. PMID 17609739.
  19. ^ a b Wouters W, Tulp MT, Bevan P (1998). "Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors". Eur J Pharmacol. 149 (3): 213–23. doi:10.1016/0014-2999(88)90651-6. PMID 2842163.
  20. ^ a b Horiuchi J, McDowall LM, Dampney RA (2008). "Role of 5-HT(1A) receptors in the lower brainstem on the cardiovascular response to dorsomedial hypothalamus activation". Auton Neurosci. 142 (1–2): 71–6. doi:10.1016/j.autneu.2008.06.004. PMID 18667366. S2CID 20878941.
  21. ^ Nalivaiko E, Ootsuka Y, Blessing WW (2005). "Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits". Am J Physiol Regul Integr Comp Physiol. 289 (2): R596–R604. doi:10.1152/ajpregu.00845.2004. PMID 15802554. S2CID 17426759.
  22. ^ a b Lucot JB. (1994). "Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin". Eur J Pharmacol. 253 (1–2): 53–60. doi:10.1016/0014-2999(94)90756-0. PMID 8013549.
  23. ^ Winstanley CA, Theobald DE, Dalley JW, Robbins TW (2005). "Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders". Neuropsychopharmacology. 30 (4): 669–682. doi:10.1038/sj.npp.1300610. PMID 15688093.
  24. ^ Ogren SO, Eriksson TM, Elvander-Tottie E, D'Addario C, Ekström JC, Svenningsson P, Meister B, Kehr J, Stiedl O (2008). "The role of 5-HT(1A) receptors in learning and memory". Behav. Brain Res. 195 (1): 54–77. doi:10.1016/j.bbr.2008.02.023. PMID 18394726. S2CID 140205386.
  25. ^ Yasuno F, Suhara T, Nakayama T, Ichimiya T, Okubo Y, Takano A, Ando T, Inoue M, Maeda J, Suzuki K (2003). "Inhibitory effect of hippocampal 5-HT1A receptors on human explicit memory". Am J Psychiatry. 160 (2): 334–40. doi:10.1176/appi.ajp.160.2.334. PMID 12562581.
  26. ^ Kennett GA, Dourish CT, Curzon G (1987). "Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression". Eur J Pharmacol. 134 (3): 265–74. doi:10.1016/0014-2999(87)90357-8. PMID 2883013.
  27. ^ Bardin L, Tarayre JP, Malfetes N, Koek W, Colpaert FC (2003). "Profound, non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain". Pharmacology. 67 (4): 182–194. doi:10.1159/000068404. PMID 12595749. S2CID 25882138.
  28. ^ a b Millan MJ, Perrin-Monneyron S (1997). "Potentiation of fluoxetine-induced penile erections by combined blockade of 5-HT1A and 5-HT1B receptors". Eur J Pharmacol. 321 (3): 11–3. doi:10.1016/S0014-2999(97)00050-2. PMID 9085055.
  29. ^ Prow MR, Martin KF, Heal DJ (1996). "8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation". Eur J Pharmacol. 317 (1): 21���8. doi:10.1016/S0014-2999(96)00693-0. PMID 8982715.
  30. ^ a b Meyer LC, Fuller A, Mitchell D (February 2006). "Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 290 (2): R405–13. doi:10.1152/ajpregu.00440.2005. PMID 16166206. S2CID 224414.
  31. ^ a b Popova NK, Amstislavskaya TG (2002). "Involvement of the 5-HT(1A) and 5-HT(1B) serotonergic receptor subtypes in sexual arousal in male mice". Psychoneuroendocrinology. 27 (5): 609–18. doi:10.1016/S0306-4530(01)00097-X. PMID 11965359. S2CID 25269315.
  32. ^ Monti JM, Jantos H (1992). "Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat". Journal of Sleep Research. 1 (3): 169–175. doi:10.1111/j.1365-2869.1992.tb00033.x. PMID 10607047.
  33. ^ Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS (2007). "A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy")". Neuroscience. 146 (2): 509–14. doi:10.1016/j.neuroscience.2007.02.032. PMID 17383105. S2CID 15617471.
  34. ^ Gudelsky GA, Koenig JI, Meltzer HY (1986). "Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors". Neuropharmacology. 25 (12): 1307–13. doi:10.1016/0028-3908(86)90101-2. PMID 2951611. S2CID 2547042.
  35. ^ Ootsuka Y, Blessing WW (2006). "Activation of 5-HT1A receptors in rostral medullary raphé inhibits cutaneous vasoconstriction elicited by cold exposure in rabbits". Brain Res. 1073–1074: 252–61. doi:10.1016/j.brainres.2005.12.031. PMID 16455061. S2CID 23178233.
  36. ^ a b c d e f g h i j k l m n o p q r s t u Pharmacology Corner > Serotonin (5-HT): receptors, agonists and antagonists By Flavio Guzmán, M.D. on 9/08/09
  37. ^ a b c d e "BRINTELLIX (vortioxetine) tablets for oral use. Full Prescribing Information, Section 12.2 (Pharmacodynamics)." Takeda Pharmaceuticals America Inc. and Lundbeck, 2013. Revised September 2013. [1]
  38. ^ Saxena, PR; Lawang, A (Oct 1985). "A comparison of cardiovascular and smooth muscle effects of 5-hydroxytryptamine and 5-carboxamidotryptamine, a selective agonist of 5-HT1 receptors". Archives Internationales de Pharmacodynamie et de Thérapie. 277 (2): 235–52. PMID 2933009.
  39. ^ Cao BJ, Rodgers RJ (October 1998). "Comparative effects of novel 5-HT1A receptor ligands, LY293284, LY315712 and LY297996, on plus-maze anxiety in mice". Psychopharmacology. 139 (3): 185–94. doi:10.1007/s002130050703. PMID 9784072. S2CID 9466299.
  40. ^ Harrison AA, Parsons LH, Koob GF, Markou A (1999). "RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist". Psychopharmacology. 141 (3): 242–50. doi:10.1007/s002130050831. PMID 10027505. S2CID 19974789.
  41. ^ Chojnacka-Wójcik E, Klodzinska A, Tatarczynska E (2005). "The anxiolytic-like effect of 5-HT1B receptor ligands in rats: a possible mechanism of action". J Pharm Pharmacol. 57 (2): 253–7. doi:10.1211/0022357055399. PMID 15720791. S2CID 20743875.
  42. ^ Lin D, Parsons LH (2002). "Anxiogenic-like effect of serotonin(1B) receptor stimulation in the rat elevated plus-maze". Pharmacol Biochem Behav. 71 (4): 581–7. doi:10.1016/S0091-3057(01)00712-2. PMID 11888549. S2CID 21610537.
  43. ^ a b Tatarczynska E, Klodzinska A, Stachowicz K, Chojnacka-Wójcik E (2004). "Effects of a selective 5-HT1B receptor agonist and antagonists in animal models of anxiety and depression". Behav Pharmacol. 15 (8): 523–34. doi:10.1097/00008877-200412000-00001. PMID 15577451. S2CID 6940756.
  44. ^ a b Eriksson TM, Madjid N, Elvander-Tottie E, Stiedl O, Svenningsson P, Ogren SO (2008). "Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission" (PDF). Neuropharmacology. 54 (7): 1041–50. doi:10.1016/j.neuropharm.2008.02.007. hdl:10616/40922. PMID 18394658. S2CID 207223573.
  45. ^ a b McCreary AC, Bankson MG, Cunningham KA (1999). "Pharmacological studies of the acute and chronic effects of (+)-3, 4-methylenedioxymethamphetamine on locomotor activity: role of 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B/1D) receptors". J Pharmacol Exp Ther. 290 (3): 965–73. PMID 10454466.
  46. ^ Amital D, Fostick L, Sasson Y, Kindler S, Amital H, Zohar J (2005). "Anxiogenic effects of Sumatriptan in panic disorder: a double-blind, placebo-controlled study". Eur Neuropsychopharmacol. 15 (3): 279–82. doi:10.1016/j.euroneuro.2004.12.002. PMID 15820416. S2CID 8382188.
  47. ^ Feuerstein TJ, Hüring H, van Velthoven V, Lücking CH, Landwehrmeyer GB (1996). "5-HT1D-like receptors inhibit the release of endogenously formed [3H]GABA in human, but not in rabbit, neocortex". Neurosci. Lett. 209 (3): 210–4. doi:10.1016/0304-3940(96)12637-9. PMID 8736648. S2CID 27376524.
  48. ^ a b Bubar MJ, Cunningham KA (2006). "Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence". Curr Top Med Chem. 6 (18): 1971–85. doi:10.2174/156802606778522131. PMID 17017968.
  49. ^ Schreiber R, Melon C, De Vry J (1998). "The role of 5-HT receptor subtypes in the anxiolytic effects of selective serotonin reuptake inhibitors in the rat ultrasonic vocalization test". Psychopharmacology. 135 (4): 383–91. doi:10.1007/s002130050526. PMID 9539263. S2CID 22677071.
  50. ^ a b Popova NK, Amstislavskaya TG (2002). "5-HT2A and 5-HT2C serotonin receptors differentially modulate mouse sexual arousal and the hypothalamo-pituitary-testicular response to the presence of a female". Neuroendocrinology. 76 (1): 28–34. doi:10.1159/000063681. PMID 12097814. S2CID 42319246.
  51. ^ a b Popa D, Léna C, Fabre V, Prenat C, Gingrich J, Escourrou P, Hamon M, Adrien J (2005). "Contribution of 5-HT2 receptor subtypes to sleep-wakefulness and respiratory control, and functional adaptations in knock-out mice lacking 5-HT2A receptors" (PDF). J. Neurosci. 25 (49): 11231–8. doi:10.1523/JNEUROSCI.1724-05.2005. PMC 6725907. PMID 16339018.
  52. ^ a b Mazzola-Pomietto P, Aulakh CS, Tolliver T, Murphy DL (1997). "Functional subsensitivity of 5-HT2A and 5-HT2C receptors mediating hyperthermia following acute and chronic treatment with 5-HT2A/2C receptor antagonists". Psychopharmacology. 130 (2): 144–51. doi:10.1007/s002130050222. PMID 9106912. S2CID 22432569.
  53. ^ Blessing WW, Seaman B (2003). "5-hydroxytryptamine(2A) receptors regulate sympathetic nerves constricting the cutaneous vascular bed in rabbits and rats". Neuroscience. 117 (4): 939–948. doi:10.1016/S0306-4522(02)00810-2. PMID 12654345. S2CID 53251590.
  54. ^ a b c McCall, R. B.; Franklin, S. R.; Hyslop, D. K.; Knauer, C. S.; Chio, C. L.; Haber, C. L.; Fitzgerald, L. W. (2001). PNU-22394, a 5-HT2C receptor agonist, reduced feeding in rodents and produces weight loss in humans (Online). Society for Neuroscience. Vol. 27. Presentation Number 309.2. San Diego, CA: Society for Neuroscience Abstracts. p. TT-45. Retrieved 18 July 2014.
  55. ^ a b c Garfield AS, Heisler LK (2009). "Pharmacological targeting of the serotonergic system for the treatment of obesity". The Journal of Physiology. 587 (1): 49–60. doi:10.1113/jphysiol.2008.164152. PMC 2670022. PMID 19029184.
  56. ^ a b c Jensen, Anders A.; Plath, Niels; Pedersen, Martin Holst Friborg; Isberg, Vignir; et al. (2013). "Design, Synthesis, and Pharmacological Characterization of N- and O-Substituted 5,6,7,8-Tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol Analogues: Novel 5-HT2A/5-HT2C Receptor Agonists with Pro-Cognitive Properties". Journal of Medicinal Chemistry. 56 (3): 1211–1227. CiteSeerX 10.1.1.691.154. doi:10.1021/jm301656h. ISSN 0022-2623. PMID 23301527.
  57. ^ Kennett GA, Bright F, Trail B, Baxter GS, Blackburn TP (1996). "Effects of the 5-HT2B receptor agonist, BW 723C86, on three rat models of anxiety". Br J Pharmacol. 117 (7): 1443–8. doi:10.1111/j.1476-5381.1996.tb15304.x. PMC 1909458. PMID 8730737.
  58. ^ Duxon MS, Kennett GA, Lightowler S, Blackburn TP, Fone KC (1997). "Activation of 5-HT2B receptors in the medial amygdala causes anxiolysis in the social interaction test in the rat". Neuropharmacology. 36 (4–5): 601–8. doi:10.1016/S0028-3908(97)00042-7. PMID 9225285. S2CID 41471226.
  59. ^ Kennett GA, Trail B, Bright F (1998). "Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated". Neuropharmacology. 37 (12): 1603–10. doi:10.1016/S0028-3908(98)00115-4. PMID 9886683. S2CID 7310462.
  60. ^ Kennett GA, Ainsworth K, Trail B, Blackburn TP (1997). "BW 723C86, a 5-HT2B receptor agonist, causes hyperphagia and reduced grooming in rats". Neuropharmacology. 36 (2): 233–9. doi:10.1016/S0028-3908(96)00171-2. PMID 9144661. S2CID 23583570.
  61. ^ Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, Carey J, Coleman RA, Baxter GS (2002). "5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro". Br J Pharmacol. 135 (5): 1144–1151. doi:10.1038/sj.bjp.0704571. PMC 1573235. PMID 11877320.
  62. ^ Kennett GA, Wood MD, Bright F, Trail B, Riley G, Holland V, Avenell KY, Stean T, Upton N, Bromidge S, Forbes IT, Brown AM, Middlemiss DN, Blackburn TP (1997). "SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist". Neuropharmacology. 36 (4–5): 609–20. doi:10.1016/S0028-3908(97)00038-5. PMID 9225286. S2CID 23032157.
  63. ^ a b Millan MJ, Brocco M, Gobert A, Dekeyne A (2005). "Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade". Psychopharmacology. 177 (4): 448–58. doi:10.1007/s00213-004-1962-z. PMID 15289999. S2CID 20866665.
  64. ^ a b Millan MJ, Brocco M, Gobert A, Dekeyne A (2008). "S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models". Psychopharmacology. 199 (4): 549–68. doi:10.1007/s00213-008-1177-9. PMID 18523738. S2CID 25063495.
  65. ^ Fujitsuka N, Asakawa A, Hayashi M, Sameshima M, Amitani H, Kojima S, Fujimiya M, Inui A (2009). "Selective serotonin reuptake inhibitors modify physiological gastrointestinal motor activities via 5-HT2c receptor and acyl ghrelin". Biol Psychiatry. 65 (9): 748–759. doi:10.1016/j.biopsych.2008.10.031. PMID 19058784. S2CID 22053616.
  66. ^ Millan MJ, Peglion JL, Lavielle G, Perrin-Monneyron S (1997). "5-HT2C receptors mediate penile erections in rats: actions of novel and selective agonists and antagonists". Eur J Pharmacol. 325 (1): 9–12. doi:10.1016/S0014-2999(97)89962-1. PMID 9151932.
  67. ^ Stancampiano R, Melis MR, Argiolas A (1994). "Penile erection and yawning induced by 5-HT1C receptor agonists in male rats: relationship with dopaminergic and oxytocinergic transmission". Eur J Pharmacol. 261 (1–2): 149–55. doi:10.1016/0014-2999(94)90313-1. PMID 8001637.
  68. ^ Frank MG, Stryker MP, Tecott LH (2002). "Sleep and sleep homeostasis in mice lacking the 5-HT2c receptor". Neuropsychopharmacology. 27 (5): 869–73. doi:10.1016/S0893-133X(02)00353-6. PMC 2452994. PMID 12431861.
  69. ^ Villalobos, Claudio A.; Bull, Paulina; Sáez, Patricio; Cassels, Bruce K.; Huidobro-Toro, J. Pablo (April 2004). "4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT2A receptor antagonists in Xenopus laevis oocytes". British Journal of Pharmacology. 141 (7): 1167–1174. doi:10.1038/sj.bjp.0705722. ISSN 0007-1188. PMC 1574890. PMID 15006903.
  70. ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. Page 187
  71. ^ Michel K, Zeller F, Langer R, Nekarda H, Kruger D, Dover TJ, Brady CA, Barnes NM, Schemann M (May 2005). "Serotonin excites neurons in the human submucous plexus via 5-HT3 receptors". Gastroenterology. 128 (5): 1317–26. doi:10.1053/j.gastro.2005.02.005. PMID 15887114. Retrieved 10 October 2014.
  72. ^ a b Pitsikas N, Brambilla A, Borsini F (1994). "Effect of DAU 6215, a novel 5-HT3 receptor antagonist, on scopolamine-induced amnesia in the rat in a spatial learning task". Pharmacol Biochem Behav. 47 (1): 95–99. doi:10.1016/0091-3057(94)90116-3. PMID 8115433. S2CID 21800364.
  73. ^ a b Smriga M, Torii K (2003). "L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 15370–5. Bibcode:2003PNAS..10015370S. doi:10.1073/pnas.2436556100. PMC 307574. PMID 14676321.
  74. ^ Kennett GA, Bright F, Trail B, Blackburn TP, Sanger GJ (1997). "Anxiolytic-like actions of the selective 5-HT4 receptor antagonists SB 204070A and SB 207266A in rats". Neuropharmacology. 36 (4–5): 707–12. doi:10.1016/S0028-3908(97)00037-3. PMID 9225297. S2CID 40341646.
  75. ^ Jean A, Conductier G, Manrique C, Bouras C, Berta P, Hen R, Charnay Y, Bockaert J, Compan V (2007). "Anorexia induced by activation of serotonin 5-HT4 receptors is mediated by increases in CART in the nucleus accumbens". Proceedings of the National Academy of Sciences of the United States of America. 104 (41): 16335–40. Bibcode:2007PNAS..10416335J. doi:10.1073/pnas.0701471104. PMC 2042207. PMID 17913892.
  76. ^ Compan V; Charnay, Y; Dusticier, N; Daszuta, A; Hen, R; Bockaert, J (2004). "Feeding disorders in 5-HT4 receptor knockout mice". J Soc Biol. 198 (1): 37–49. doi:10.1051/jbio/2004198010037. PMID 15146954.
  77. ^ a b Meneses A, Hong E (1997). "Effects of 5-HT4 receptor agonists and antagonists in learning". Pharmacol Biochem Behav. 56 (3): 347–51. doi:10.1016/S0091-3057(96)00224-9. PMID 9077568. S2CID 11866740.
  78. ^ a b Fontana DJ, Daniels SE, Wong EH, Clark RD, Eglen RM (1997). "The effects of novel, selective 5-hydroxytryptamine (5-HT)4 receptor ligands in rat spatial navigation". Neuropharmacology. 36 (4–5): 689–96. doi:10.1016/S0028-3908(97)00055-5. PMID 9225295. S2CID 46510811.
  79. ^ Fontana DJ, Daniels SE, Wong EH, Clark RD, Eglen RM (1998). "Role of 5-HT4 receptors in the mouse passive avoidance test". J Pharmacol Exp Ther. 286 (3): 1115–21. PMID 9732367.
  80. ^ Lucas, G.; Rymar, V. V.; Du, J.; Mnie-Filali, O.; Bisgaard, C.; Manta, S.; Lambas-Senas, L.; Wiborg, O.; Haddjeri, N.; Piñeyro, G.; Sadikot, A. F.; Debonnel, G. (2007). "Serotonin4 (5-HT4) Receptor Agonists Are Putative Antidepressants with a Rapid Onset of Action". Neuron. 55 (5): 712–725. doi:10.1016/j.neuron.2007.07.041. PMID 17785179. S2CID 14558104.
  81. ^ Duman, R. S. (2007). "A Silver Bullet for the Treatment of Depression?". Neuron. 55 (5): 679–681. doi:10.1016/j.neuron.2007.08.011. PMID 17785173.
  82. ^ Manzke, T. (2003). "5-HT4(a) Receptors Avert Opioid-Induced Breathing Depression Without Loss of Analgesia". Science. 301 (5630): 226–229. Bibcode:2003Sci...301..226M. doi:10.1126/science.1084674. ISSN 0036-8075. PMID 12855812. S2CID 13641423.
  83. ^ Nelson DL (2004). "5-HT5 receptors". Curr Drug Targets CNS Neurol Disord. 3 (1): 53–8. doi:10.2174/1568007043482606. PMID 14965244.
  84. ^ a b Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (2005). "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro". Brain Res Mol Brain Res. 138 (2): 191–7. doi:10.1016/j.molbrainres.2005.04.009. PMC 5805132. PMID 15921820.
  85. ^ Wesolowska A (February 2008). "The anxiolytic-like effect of the selective 5-HT6 receptor antagonist SB-399885: the impact of benzodiazepine receptors". European Journal of Pharmacology. 580 (3): 355–60. doi:10.1016/j.ejphar.2007.11.022. PMID 18096153.
  86. ^ a b Wesolowska A, Nikiforuk A (April 2007). "Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression". Neuropharmacology. 52 (5): 1274–83. doi:10.1016/j.neuropharm.2007.01.007. PMID 17320917. S2CID 22664564.
  87. ^ Hirst WD, Stean TO, Rogers DC, Sunter D, Pugh P, Moss SF, Bromidge SM, Riley G, Smith DR, Bartlett S, Heidbreder CA, Atkins AR, Lacroix LP, Dawson LA, Foley AG, Regan CM, Upton N (December 2006). "SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models". European Journal of Pharmacology. 553 (1–3): 109–19. doi:10.1016/j.ejphar.2006.09.049. PMID 17069795.
  88. ^ a b Perez-García G, Meneses A (July 2005). "Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task". Pharmacology Biochemistry and Behavior. 81 (3): 673–82. doi:10.1016/j.pbb.2005.05.005. PMID 15964617. S2CID 19789219.
  89. ^ Wesolowska A, Nikiforuk A (March 2008). "The selective 5-HT(6) receptor antagonist SB-399885 enhances anti-immobility action of antidepressants in rats". European Journal of Pharmacology. 582 (1–3): 88–93. doi:10.1016/j.ejphar.2007.12.013. PMID 18234190.
  90. ^ "Target Schizophrenia - Possible future developments". The Association of the British Pharmaceutical Industry. Archived from the original on 2008-06-12. Retrieved 2008-04-11.
  91. ^ a b c Hedlund PB, Huitron-Resendiz S, Henriksen SJ, Sutcliffe JG (November 2005). "5-HT7 receptor inhibition and inactivation induce antidepressantlike behavior and sleep pattern". Biological Psychiatry. 58 (10): 831–7. doi:10.1016/j.biopsych.2005.05.012. PMID 16018977. S2CID 10998014.
  92. ^ a b Wesolowska A, Nikiforuk A, Stachowicz K, Tatarczynska E (September 2006). "Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression". Neuropharmacology. 51 (3): 578–86. doi:10.1016/j.neuropharm.2006.04.017. PMID 16828124. S2CID 39928418.
  93. ^ Gasbarri A, Cifariello A, Pompili A, Meneses A (December 2008). "Effect of 5-HT(7) antagonist SB-269970 in the modulation of working and reference memory in the rat". Behavioural Brain Research. 195 (1): 164–70. doi:10.1016/j.bbr.2007.12.020. PMID 18308404. S2CID 12910296.
  94. ^ Liy-Salmeron G, Meneses A (2008). "Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model". Hippocampus. 18 (9): 965–74. doi:10.1002/hipo.20459. PMID 18570192. S2CID 20937527.
  95. ^ a b Bonaventure P, Kelly L, Aluisio L, Shelton J, Lord B, Galici R, Miller K, Atack J, Lovenberg TW, Dugovic C (2007). "Selective blockade of 5-hydroxytryptamine (5-HT)7 receptors enhances 5-HT transmission, antidepressant-like behavior, and rapid eye movement sleep suppression induced by citalopram in rodents". J Pharmacol Exp Ther. 321 (2): 690–8. doi:10.1124/jpet.107.119404. PMID 17314195. S2CID 14579645.
  96. ^ Thomas DR, Melotto S, Massagrande M, Gribble AD, Jeffrey P, Stevens AJ, Deeks NJ, Eddershaw PJ, Fenwick SH, Riley G, Stean T, Scott CM, Hill MJ, Middlemiss DN, Hagan JJ, Price GW, Forbes IT (2003). "SB-656104-A, a novel selective 5-HT7 receptor antagonist, modulates REM sleep in rats". Br J Pharmacol. 139 (4): 705–14. doi:10.1038/sj.bjp.0705290. PMC 1573887. PMID 12812993.
  97. ^ Davies MA, Sheffler DJ, Roth BL. Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology. CNS Drug Reviews [Internet]. 2004 [cited 2013 Aug 4];10(4):317–36. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00030.x/pdf
  98. ^ "HTR2C 5-hydroxytryptamine receptor 2C [ Homo sapiens (human) ]". NCBI. 19 Mar 2017. Retrieved 26 Mar 2017.
  99. ^ Bar-Shira O, Maor R, Chechik G (2015). "Gene Expression Switching of Receptor Subunits in Human Brain Development". PLOS Computational Biology. 11 (12): e1004559. Bibcode:2015PLSCB..11E4559B. doi:10.1371/journal.pcbi.1004559. PMC 4670163. PMID 26636753.
  100. ^ Saxena, P.R.; De Vries, P.; Villalón, C.M. (1998). "5-HT 1 -like receptors: A time to bid goodbye". Trends in Pharmacological Sciences. 19 (8): 311–316. doi:10.1016/S0165-6147(98)01228-0. PMID 9745358.

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