Target Information

Target General Information

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Target ID

T75984 (Former ID: TTDI01743)

Target Name

5-HT 2 receptor (5HT2R)

Synonyms

Serotonin receptor 2; 5-hydroxytryptamine receptor 2; 5-HT2 receptor

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Depression [ICD-11: 6A70-6A7Z]

Hypertension [ICD-11: BA00-BA04]

Psychotic disorder [ICD-11: 6A20-6A25]

Function

G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.

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BioChemical Class

GPCR rhodopsin

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 4 Approved Drugs

Cyclobenzaprine

Drug Info

Approved

Depression

[2], [3]

Ketanserin

Drug Info

Approved

Hypertension

[4], [5]

Mianserin

Drug Info

Approved

Depression

[6], [7]

Perospirone

Drug Info

Approved

Psychotic disorder

[8], [9]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

Bis(olanzapine) pamoate monohydrate

Drug Info

Phase 3

Psychotic disorder

[9]

Nexopamil

Drug Info

Phase 2

Hypertension

[10]

TGOF02N

Drug Info

Phase 2

Schizophrenia

[11]

TGWOOAA

Drug Info

Phase 2

Social phobia

[12]

AMAP-102

Drug Info

Phase 1

Arthritis

[13]

Discontinued Drug(s)

[+] 11 Discontinued Drugs

Ritanserin

Drug Info

Discontinued in Phase 3

Anxiety disorder

[14], [15]

ICI-170809

Drug Info

Discontinued in Phase 2

Anxiety disorder

[16]

SUN-C5174

Drug Info

Discontinued in Phase 2

Peripheral vascular disease

[17]

Beloxepin

Drug Info

Discontinued in Phase 1

Depression

[18]

SUN-9221

Drug Info

Discontinued in Phase 1

Hypertension

[19]

AHR-16303B

Drug Info

Terminated

Hypertension

[20]

Dotarizine

Drug Info

Terminated

Migraine

[21]

E-2040

Drug Info

Terminated

Schizophrenia

[22]

Emopamil

Drug Info

Terminated

Cerebrovascular ischaemia

[23]

MDL-28133A

Drug Info

Terminated

Thrombosis

[24]

NPC-18166

Drug Info

Terminated

Psychotic disorder

[25]

Mode of Action

[+] 3 Modes of Action

Antagonist

[+] 9 Antagonist drugs

Cyclobenzaprine

Drug Info

[26]

Ketanserin

Drug Info

[27]

Mianserin

Drug Info

[28], [29], [30], [31]

TGWOOAA

Drug Info

[34]

AMAP-102

Drug Info

[35]

Heterocyclic-tetracyclic tetrahydrofuran derivative 1

Drug Info

[36]

Ritanserin

Drug Info

[37], [38], [39], [40]

SUN-C5174

Drug Info

[42]

Metrenperone

Drug Info

[48], [49], [50], [51]

Modulator

[+] 13 Modulator drugs

Perospirone

Drug Info

[1], [9]

Bis(olanzapine) pamoate monohydrate

Drug Info

[9]

Nexopamil

Drug Info

[10]

TGOF02N

Drug Info

[33]

ICI-170809

Drug Info

[41]

Beloxepin

Drug Info

[43]

SUN-9221

Drug Info

[44]

AHR-16303B

Drug Info

[20]

Dotarizine

Drug Info

[21]

E-2040

Drug Info

[45]

Emopamil

Drug Info

[23]

MDL-28133A

Drug Info

[46]

NPC-18166

Drug Info

[47]

Inhibitor

[+] 1 Inhibitor drugs

FKB01MD

Drug Info

[32]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 5 KEGG Pathways

Calcium signaling pathway

Neuroactive ligand-receptor interaction

Gap junction

Serotonergic synapse

Inflammatory mediator regulation of TRP channels

References

Top

REF 1

Pharmacological effects of zotepine and other antipsychotics on the central 5-HT2 receptors. Pharmacopsychiatry. 1993 Mar;26(2):53-8.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7152).

REF 3

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021777.

REF 4

REF 5

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 6

REF 7

Emerging treatments for depression. Expert Opin Pharmacother. 2006 Dec;7(17):2323-39.

REF 8

REF 9

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 10

Inhibition by the combined Ca2+ and 5-HT2 receptor antagonist nexopamil (LU 49938) of intracoronary thrombus formation in a canine model of arterial stenosis and intimal damage. J Cardiovasc Pharmacol. 1993 Nov;22(5):687-94.

REF 11

Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.

REF 12

Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.

REF 13

ClinicalTrials.gov (NCT00995605) AMAP102 - Safety, Tolerability and Pharmacokinetics in Healthy Subjects. U.S. National Institutes of Health.

REF 14

REF 15

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000237)

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001766)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012828)

REF 18

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001334)

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006767)

REF 20

AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels. J Cardiovasc Pharmacol. 1991 Jan;17(1):41-53.

REF 21

Vasostabilizing effect of Dotarizine (Ca(2+)-channel blocker) on cerebrovascular reactivity in rabbits. Neurol Res. 2000 Mar;22(2):229-32.

REF 22

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009126)

REF 23

Calcium entry and 5-HT2 receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats. Br J Pharmacol. 1996 Mar;117(6):1348-54.

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002814)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004563)

REF 26

Torticollis under Cyclobenzaprine. Pharmacology. 2009 Jul 8;84(2):91-92.

REF 27

Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine. Am J Physiol Lung Cell Mol Physiol. 2004 Mar;286(3):L531-8.

REF 28

5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats. Neurosci Lett. 2008 Jan 17;430(3):191-6.

REF 29

5-HT2 and 5-HT3 receptors in the lateral parabrachial nucleus mediate opposite effects on sodium intake. Neuroscience. 2007 Jun 8;146(4):1453-61.

REF 30

Lack of effect of some dopamine and non-dopamine receptor ligands on amphetamine-induced changes in the rat brain neuropeptide Y system. Pharmacol Rep. 2005 Nov-Dec;57(6):850-5.

REF 31

5-HT2 receptor antagonists given in the acute withdrawal from daily cocaine injections can reverse established sensitization. Eur J Pharmacol. 2002 Oct 25;453(2-3):255-63.

REF 32

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 33

Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.

REF 34

Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.

REF 35

Clinical pipeline report, company report or official report of Anamar.

REF 36

Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.

REF 37

Characterization of contractile 5-hydroxytryptamine receptor subtypes in the in situ autoperfused kidney in the anaesthetized rat. Eur J Pharmacol. 2008 Sep 11;592(1-3):133-7.

REF 38

Hypersensitivity of 5-HT2 receptors in OCD patients. An increased prolactin response after a challenge with meta-chlorophenylpiperazine and pre-tre... J Psychiatr Res. 2008 Sep;42(11):894-901.

REF 39

Effects of antipsychotics and reference monoaminergic ligands on marble burying behavior in mice. Behav Pharmacol. 2008 Mar;19(2):145-52.

REF 40

Combined treatment of portal hypertension with ritanserin and propranolol in conscious and unrestrained cirrhotic rats. Hepatology. 1992 May;15(5):878-82.

REF 41

5-HT2 receptor blockade by ICI 170,809 does not affect the inhibitory effect of the 5-HT1A receptor ligand gepirone on neuroleptic-induced catalepsy. Braz J Med Biol Res. 1994 Oct;27(10):2437-41.

REF 42

Synthesis and serotonin 2 (5-HT2) receptor antagonist activity of 5-aminoalkyl-substituted pyrrolo[3,2-c]azepines and related compounds. Chem Pharm Bull (Tokyo). 2000 May;48(5):623-35.

REF 43

WO patent application no. 2009,1055,07, Beloxepin, its enantiomers, and analogs thereof for the treatment of pain.

REF 44

Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity. Chem Pharm Bull (Tokyo). 1999 Feb;47(2):246-56.

REF 45

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009126)

REF 46

Effects of MDL 28,133A, a 5-HT2 receptor antagonist, on platelet aggregation and coronary thrombosis in dogs. J Cardiovasc Pharmacol. 1994 Nov;24(5):761-72.

REF 47

WO patent application no. 2004,0825,84, 5ht2c receptor antagonists in the treatment of schizophrenia.

REF 48

Cardiovascular response to intravenous administration of 5-hydroxytryptamine after type-2 receptor blockade, by metrenperone, in healthy calves. Vet J. 1999 Jan;157(1):31-7.

REF 49

Pulmonary response to intravenous administration of 5-hydroxytryptamine after type-2 receptor blockade in healthy calves. Am J Vet Res. 1993 Jan;54(1):168-73.

REF 50

Induction of serotonin-S2 receptor blockade during early or late stage of acute respiratory distress syndrome in double-muscled calves: a comparative study. Zentralbl Veterinarmed A. 1993 May;40(4):241-8.

REF 51

Efficiency of 5-hydroxytryptamine receptor blockade as therapeutic measure during acute respiratory distress syndrome in double-muscled cattle. Zentralbl Veterinarmed A. 1993 Apr;40(3):185-93.

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