Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTYSN63)

• DTT Name: 5-HT 2 receptor (5HT2R)
• Synonyms: Serotonin receptor 2; 5-hydroxytryptamine receptor 2; 5-HT2 receptor
• Gene Name: 5HT2R
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NOUNIPROTAC
• TTD ID: T75984
• 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.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Gap junction (hsa04540)
  Serotonergic synapse (hsa04726)
  Inflammatory mediator regulation of TRP channels (hsa04750)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cyclobenzaprine	DM1YBRM	Depression	6A70-6A7Z	Approved	[2]
Ketanserin	DMVLMW6	Hypertension	BA00-BA04	Approved	[3]
Mianserin	DMVKA4O	Depression	6A70-6A7Z	Approved	[4]
Perospirone	DMVHJLX	Psychotic disorder	6A20-6A25	Approved	[1]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bis(olanzapine) pamoate monohydrate	DME76AP	Psychotic disorder	6A20-6A25	Phase 3	[5]
FKB01MD	DM2O7NM	N. A.	N. A.	Phase 2	[6]
Nexopamil	DML5S71	Hypertension	BA00-BA04	Phase 2	[7]
TGOF02N	DMQ6ANE	Schizophrenia	6A20	Phase 2	[8]
TGWOOAA	DMI57ZA	Generalized anxiety disorder	6B00	Phase 2	[9]
AMAP-102	DM7CD8Z	Arthritis	FA20	Phase 1	[10]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Heterocyclic-tetracyclic tetrahydrofuran derivative 1	DMNJVR6	N. A.	N. A.	Patented	[11]

11 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ritanserin	DM0X36Y	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[12]
ICI-170809	DMKUVZO	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[13]
SUN-C5174	DMZ8VI0	Peripheral vascular disease	BD4Z	Discontinued in Phase 2	[14]
Beloxepin	DMCOKFY	Depression	6A70-6A7Z	Discontinued in Phase 1	[15]
SUN-9221	DM6BO7R	Hypertension	BA00-BA04	Discontinued in Phase 1	[16]
AHR-16303B	DMJZ48W	Hypertension	BA00-BA04	Terminated	[17]
Dotarizine	DM6Q05K	Migraine	8A80	Terminated	[18]
E-2040	DMZWU8V	Schizophrenia	6A20	Terminated	[19]
Emopamil	DMW210B	Cerebrovascular ischaemia	8B1Z	Terminated	[20]
MDL-28133A	DM6X4IT	Thrombosis	DB61-GB90	Terminated	[21]
NPC-18166	DMAIH90	Psychotic disorder	6A20-6A25	Terminated	[22]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metrenperone	DM70RDZ	Discovery agent	N.A.	Investigative	[23]

References

• [1] Pharmacological effects of zotepine and other antipsychotics on the central 5-HT2 receptors. Pharmacopsychiatry. 1993 Mar;26(2):53-8.
• [2] Torticollis under Cyclobenzaprine. Pharmacology. 2009 Jul 8;84(2):91-92.
• [3] Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine. Am J Physiol Lung Cell Mol Physiol. 2004 Mar;286(3):L531-8.
• [4] 5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats. Neurosci Lett. 2008 Jan 17;430(3):191-6.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] 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.
• [8] Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.
• [9] Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.
• [10] Clinical pipeline report, company report or official report of Anamar.
• [11] Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] WO patent application no. 2009,1055,07, Beloxepin, its enantiomers, and analogs thereof for the treatment of pain.
• [16] 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.
• [17] AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels. J Cardiovasc Pharmacol. 1991 Jan;17(1):41-53.
• [18] Vasostabilizing effect of Dotarizine (Ca(2+)-channel blocker) on cerebrovascular reactivity in rabbits. Neurol Res. 2000 Mar;22(2):229-32.
• [19] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009126)
• [20] 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.
• [21] 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.
• [22] WO patent application no. 2004,0825,84, 5ht2c receptor antagonists in the treatment of schizophrenia.
• [23] 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.