Lumateperone

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Identification

Summary

Lumateperone is a novel 2nd generation antipsychotic used to manage both positive and negative symptoms in patients with schizophrenia.

Brand Names

Caplyta

Generic Name

Lumateperone

DrugBank Accession Number

DB06077

Background

Schizophrenia is a complex mental illness and impacts approximately 1% of the population.⁷ Although there are several antipsychotics including aripiprazole, paliperidone and clozapine available for clinical use, they are generally accompanied by significant metabolic and/or neurological adverse effects.¹

Lumateperone is a newly approved 2nd generation antipsychotic currently indicated for the treatment of schizophrenia.¹ It has a unique receptor binding profile and differs from other antipsychotics in that it modulates glutamate, serotonin and dopamine, which are all neurotransmitters that contribute to the pathophysiology of schizophrenia.^1,5

The data so far indicates that lumateperone can alleviate both positive and negative symptoms of schizophrenia.¹ Further, not only is the new antipsychotic selective for dopamine (D2) receptors in the mesolimbic and mesocortical brain regions, but it also has minimal off-target activity.¹ Both characteristics lend to a more favourable adverse effect profile and ultimately safer drug.^1,8

Type

Small Molecule

Groups

Approved, Investigational

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Lumateperone (DB06077)

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Weight

Average: 393.506
Monoisotopic: 393.221640697

Chemical Formula

C₂₄H₂₈FN₃O

Synonyms

• Lumateperone

External IDs

• ITI 007
• ITI-007
• ITI-722
• ITI007

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Pharmacology

Indication

Lumateperone is approved for the treatment of schizophrenia in adults.⁶ It is also approved for the treatment of depressive episodes associated with bipolar disorder (i.e. bipolar depression) in adults, as monotherapy and/or adjunctive therapy with lithium or valproate.⁶

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to manage	Depressive episodes		••••••••••••	•••••		•••••••
Used in combination to manage	Depressive episodes	Regimen in combination with: Valproic acid (DB00313)	••••••••••••	•••••		•••••••
Used in combination to manage	Depressive episodes		••••••••••••	•••••		•••••••
Used in combination to manage	Depressive episodes	Regimen in combination with: Valproic acid (DB00313)	••••••••••••	•••••		•••••••
Management of	Depressive episodes		••••••••••••	•••••		•••••••

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Pharmacodynamics

Lumateperone, also known as ITI-007, is an atypical antipsychotic that has proven to be effective in the treatment of schizophrenia.¹ Lumateperone's receptor binding profile is unique, allowing it to target schizophrenia related symptoms while minimizing adverse effects.^1,5 In contrast to other second generation antipsychotics such as lurasidone and brexpiprazole, lumateperone behaves as a partial agonist and as an antagonist at pre and postynaptic dopamine (D2) receptors respectively.¹

Patients with moderate or severe hepatic impairment (Child-Pugh class B or C) tend to have higher plasma concentrations of lumateperone than those with normal hepatic function. For this reason, patients with moderate or severe hepatic impairment should receive half the recommended daily dosage.⁶

Mechanism of action

There is much to learn about the pathophysiology of schizophrenia; however, dopamine abnormalities, specifically in the prefrontal and mesolimbic brain regions, are consistent in people with schizophrenia.² In addition to dopamine, other neurotransmitters such as serotonin, glutamate, GABA and acetylcholine are thought to play a role.²

Lumateperone is unique among second generation antipsychotics based on its target profile and dopamine D2 receptor occupancy.^1,3 Unlike other antipsychotics, lumateperone has partial agonist activity at presynaptic dopamine (D2) receptors, resulting in reduced presynaptic release of dopamine, and antagonistic activity at postsynaptic dopamine (D2) receptors.³ These characteristics allow lumateperone to efficiently reduce dopamine signaling.³

Lumateperone also targets dopamine (D1) receptors, and a useful secondary result of D1 activation is increased glutamatergic N-methyl-D-aspartate (NMDA) GluN2B receptor phosphorylation.^1,3,4 This is significant since NMDA mediated glutamate signaling appears to be impaired in patients who have schizophrenia.¹

Finally, lumateperone is capable of modulating serotonin by inhibiting serotonin transporters (SERT), and by behaving as a 5-HT2A receptor antagonist.³

Target	Actions	Organism
ASodium-dependent serotonin transporter	inhibitor	Humans
AGlutamate receptor ionotropic, NMDA 2B	Not Available	Humans
A5-hydroxytryptamine receptor 2A	antagonist	Humans
AD(2) dopamine receptor	partial agonist	Humans
UD(1A) dopamine receptor	Not Available	Humans

Absorption

Lumateperone is able to permeate multidrug resistance protein 1 (MDR1) and is very lipophilic at a pH of 7.4, which are characteristics that allow the antipsychotic to be absorbed in the small intestine and the blood brain barrier.¹ Tmax occurs 3-4 hours after oral administration.¹

Volume of distribution

The volume of distribution of lumateperone is approximately 4.1 L/Kg after intravenous administration.⁶

Protein binding

Lumateperone is approximately 97.4% plasma protein bound.^1,6

Metabolism

Lumateperone is extensively metabolized. The carbonyl side chain is reduced by ketone reductase to produce the primary active metabolite.^1,3 Cytochrome P450 3A4 enzymes metabolize lumateperone to 2 metabolites: the active N-desmethylated carbonyl metabolite (IC200161) or the N-desmethylated alcohol metabolite (IC200565).^1,3

Hover over products below to view reaction partners

• Lumateperone
  • ICI200131
  • IC200161
  • IC200565

Route of elimination

Due to it's molecular weight, virtually all unchanged lumateperone is excreted in the feces.^6,1 Lumateperone's metabolites are very water soluble which is a property that allows for complete elimination.¹ Approximately 58% of a lumateperone dose can be recovered in the urine, while 29% can be recovered in the feces.⁶

Half-life

Lumateperone's half life is reported to be between 13 to 18 hours.^1,6 The reported half lives of the metabolites ICI200161 and ICI200131, are 20 and 21 hours respectively.¹

Clearance

Lumateperone's clearance is estimated to be 27.9 L/hour.⁶

Adverse Effects

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Toxicity

Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Available data from case reports on lumateperone use in pregnant women are insufficient to establish any drug associated risks for birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including lumateperone, during pregnancy. In animal reproduction studies, no malformations were observed with oral administration of lumateperone to pregnant rats and rabbits during organogenesis at doses up to 2.4 and 9.7 times, respectively, the maximum recommended human dose (MRHD) of 42 mg/day on a mg/m2 basis. When pregnant rats were administered lumateperone during the period of organogenesis through lactation, the number of perinatal deaths of pups was increased at 4.9 times the MRHD, with no adverse effects on pups at 2.4 times the MRHD.⁹

Based on findings from animal studies, lumateperone may impair male and female fertility.⁹

No specific antidotes for CAPLYTA are known. In managing overdose, provide supportive care, including close medical supervision and monitoring and consider the possibility of multiple drug involvement. In case of overdose, consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org).⁹

Lifetime carcinogenicity studies were conducted in rats and mice, and results showed no carcinogenic potential in either species. No evidence of mutagenic potential was found in the in vitro bacterial reverse mutation assay (Ames test) and the mouse lymphoma test without metabolic activation. Lumateperone was positive in the Ames test only in the presence of metabolic activation and only in the TA1537 strain and was positive in the mouse lymphoma test only in the presence of metabolic activation and only at high concentrations that inhibited cell growth; together these results were thought to be related to solubility limits and/or nonspecific effects on cellular function. Lumateperone was negative for clastogenic activity in the in vivo micronucleus assay in rats and was not genotoxic in the in vivo Comet assay in rats.⁹

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	The risk or severity of CNS depression can be increased when Lumateperone is combined with 1,2-Benzodiazepine.
Abametapir	The serum concentration of Lumateperone can be increased when it is combined with Abametapir.
Acetaminophen	The serum concentration of Lumateperone can be decreased when it is combined with Acetaminophen.
Acetazolamide	The risk or severity of CNS depression can be increased when Acetazolamide is combined with Lumateperone.
Acetophenazine	The risk or severity of adverse effects can be increased when Lumateperone is combined with Acetophenazine.

Food Interactions

• Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of lumateperone, which may increase its serum concentration.
• Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of lumateperone, causing a reduction in its serum concentration.
• Take with food. Administration with food reduces the Cmax by 33% and prolongs the Tmax by one hour.

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Lumateperone tosylate	JIE88N006O	1187020-80-9	LHAPOGAFBLSJJQ-GUTACTQSSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Caplyta	Capsule	21 mg/1	Oral	Intra-Cellular Therapies, Inc	2022-08-09	Not applicable
Caplyta	Capsule	42 mg/1	Oral	REMEDYREPACK INC.	2022-08-24	Not applicable
Caplyta	Capsule	42 mg/1	Oral	Intra-Cellular Therapies, Inc	2020-02-01	Not applicable
Caplyta	Capsule	10.5 mg/1	Oral	Intra-Cellular Therapies, Inc	2022-08-09	Not applicable

Categories

ATC Codes

N05AD10 — Lumateperone

• N05AD — Butyrophenone derivatives
• N05A — ANTIPSYCHOTICS
• N05 — PSYCHOLEPTICS
• N — NERVOUS SYSTEM

Drug Categories

• Antidepressive Agents
• Antipsychotic Agents
• Antipsychotic Agents (Second Generation [Atypical])
• Butyrophenone Derivatives
• Central Nervous System Depressants
• Cytochrome P-450 CYP1A2 Substrates
• Cytochrome P-450 CYP2C8 Substrates
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Substrates
• Dopamine Agonists
• Dopamine Antagonists
• Dopamine D2 Receptor Agonists
• Heterocyclic Compounds, Fused-Ring
• Nervous System
• Neurotoxic agents
• Psycholeptics
• Serotonin 5-HT2 Receptor Antagonists
• Serotonin 5-HT2A Receptor Antagonists
• Serotonin Agents
• Serotonin Modulators
• Serotonin Receptor Antagonists
• UGT1A1 Substrates
• UGT1A4 substrates

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Carbonyl compounds

Direct Parent

Alkyl-phenylketones

Alternative Parents

Phenylbutylamines / Butyrophenones / Indoles and derivatives / Aryl alkyl ketones / Benzoyl derivatives / Dialkylarylamines / Aralkylamines / Fluorobenzenes / Piperidines / Aryl fluorides / Gamma-amino ketones / Trialkylamines / Azacyclic compounds / Organofluorides / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives

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Substituents

Alkyl-phenylketone / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Benzoyl / Butyrophenone / Dialkylarylamine / Fluorobenzene / Gamma-aminoketone / Halobenzene / Hydrocarbon derivative / Indole or derivatives / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organofluoride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organopnictogen compound / Phenylbutylamine / Piperidine / Tertiary aliphatic amine / Tertiary aliphatic/aromatic amine / Tertiary amine

show 20 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Affected organisms

Not Available

Chemical Identifiers

UNII

70BSQ12069

CAS number

313368-91-1

InChI Key

HOIIHACBCFLJET-SFTDATJTSA-N

InChI

InChI=1S/C24H28FN3O/c1-26-14-15-28-21-11-13-27(16-20(21)19-4-2-5-22(26)24(19)28)12-3-6-23(29)17-7-9-18(25)10-8-17/h2,4-5,7-10,20-21H,3,6,11-16H2,1H3/t20-,21-/m0/s1

IUPAC Name

1-(4-fluorophenyl)-4-[(10R,15S)-4-methyl-1,4,12-triazatetracyclo[7.6.1.0^{5,16}.0^{10,15}]hexadeca-5(16),6,8-trien-12-yl]butan-1-one

SMILES

[H][C@]12CCN(CCCC(=O)C3=CC=C(F)C=C3)C[C@@]1([H])C1=CC=CC3=C1N2CCN3C

References

General References

1. Vyas P, Hwang BJ, Brasic JR: An evaluation of lumateperone tosylate for the treatment of schizophrenia. Expert Opin Pharmacother. 2019 Nov 30:1-7. doi: 10.1080/14656566.2019.1695778. [Article]
2. Brisch R, Saniotis A, Wolf R, Bielau H, Bernstein HG, Steiner J, Bogerts B, Braun K, Jankowski Z, Kumaratilake J, Henneberg M, Gos T: The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front Psychiatry. 2014 May 19;5:47. doi: 10.3389/fpsyt.2014.00047. eCollection 2014. [Article]
3. Vanover KE, Davis RE, Zhou Y, Ye W, Brasic JR, Gapasin L, Saillard J, Weingart M, Litman RE, Mates S, Wong DF: Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Neuropsychopharmacology. 2019 Feb;44(3):598-605. doi: 10.1038/s41386-018-0251-1. Epub 2018 Oct 26. [Article]
4. Kumar B, Kuhad A, Kuhad A: Lumateperone: a new treatment approach for neuropsychiatric disorders. Drugs Today (Barc). 2018 Dec;54(12):713-719. doi: 10.1358/dot.2018.54.12.2899443. [Article]
5. Ceskova E, Silhan P: Novel treatment options in depression and psychosis. Neuropsychiatr Dis Treat. 2018 Mar 13;14:741-747. doi: 10.2147/NDT.S157475. eCollection 2018. [Article]
6. FDA Approved Drug Products: Caplyta (lumateperone) capsules for oral use [Link]
7. 24. The Clinical Development of Lumateperone (ITI-007) for the Treatment of Schizophrenia [Link]
8. S44. Lumateperone (ITI-007) for the Treatment of Schizophrenia: Placebo-Controlled Clinical Trials and an Open-Label Safety Switching Study [Link]
9. FDA Approved Drug Products: Caplyta (lumateperone) capsules for oral use (June 2023) [Link]

External Links

PubChem Compound

21302490

PubChem Substance

310264860

ChemSpider

19328801

RxNav

2275602

ChEMBL

CHEMBL3306803

ZINC

ZINC000116262036

PDBe Ligand

92S

Wikipedia

Lumateperone

PDB Entries

7wc8

Clinical Trials

Clinical Trials

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
4	Recruiting	Treatment	Schizoaffective Disorders / Schizophrenia	1	somestatus	stop reason	just information to hide
4	Terminated	Other	Psychosis	1	somestatus	stop reason	just information to hide
3	Active Not Recruiting	Treatment	Schizophrenia	1	somestatus	stop reason	just information to hide
3	Completed	Treatment	Depression, Bipolar	3	somestatus	stop reason	just information to hide
3	Completed	Treatment	Depression, Bipolar / Major Depressive Disorder (MDD)	1	somestatus	stop reason	just information to hide

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Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Capsule	Oral	10.5 mg/1
Capsule	Oral	21 mg/1
Capsule	Oral	42 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US10464938	No	2019-11-05	2028-03-12
US8648077	No	2014-02-11	2029-12-01
US9616061	No	2017-04-11	2029-05-27
US7183282	No	2007-02-27	2020-06-15
US9586960	No	2017-03-07	2029-03-12
US8598119	No	2013-12-03	2029-12-28
USRE39680	No	2007-06-05	2020-06-15
US9199995	No	2015-12-01	2029-03-12
US9956227	No	2018-05-01	2034-12-03
US10695345	No	2020-06-30	2039-08-30
US10960009	No	2021-03-30	2034-12-03
USRE48839	No	2021-12-07	2029-12-28
USRE48825	No	2021-11-23	2029-03-12
US10117867	No	2018-11-06	2029-05-27
US11026951	No	2021-06-08	2034-12-03
US11052084	No	2021-07-06	2039-08-30
US11690842	No	2019-08-30	2039-08-30
US11753419	No	2020-12-10	2040-12-10
US11806348	No	2019-08-30	2039-08-30
US9168258	No	2009-05-27	2029-05-27
US11980617	No	2019-10-27	2039-10-27
US12070459	No	2019-08-30	2039-08-30

Properties

State

Solid

Experimental Properties

Property	Value	Source
logP	2.328	http://www.chemspider.com/Chemical-Structure.19328801.html

Predicted Properties

Property	Value	Source
Water Solubility	0.0805 mg/mL	ALOGPS
logP	3.87	ALOGPS
logP	3.59	Chemaxon
logS	-3.7	ALOGPS
pKa (Strongest Acidic)	16.61	Chemaxon
pKa (Strongest Basic)	8.47	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	4	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	26.79 Å2	Chemaxon
Rotatable Bond Count	5	Chemaxon
Refractivity	116.42 m3·mol-1	Chemaxon
Polarizability	44.27 Å3	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-0009000000-130df7fcb46781ce351b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-00dl-0009000000-cbfee8439271c711fd3c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-0109000000-aa3818c44f556d727632
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-0009000000-e3a3093640dba70d049a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00sl-1479000000-9d2d1a225edbb7aa69d7
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0200-1159000000-1bb07e18925223ead05a
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	201.90852	predicted	DeepCCS 1.0 (2019)
[M+H]+	204.35316	predicted	DeepCCS 1.0 (2019)
[M+Na]+	212.36826	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. Sodium-dependent serotonin transporter

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity)

Specific Function

actin filament binding

Gene Name

SLC6A4

Uniprot ID

P31645

Uniprot Name

Sodium-dependent serotonin transporter

Molecular Weight

70324.165 Da

References

1. Vanover KE, Davis RE, Zhou Y, Ye W, Brasic JR, Gapasin L, Saillard J, Weingart M, Litman RE, Mates S, Wong DF: Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Neuropsychopharmacology. 2019 Feb;44(3):598-605. doi: 10.1038/s41386-018-0251-1. Epub 2018 Oct 26. [Article]

Details2. Glutamate receptor ionotropic, NMDA 2B

Kind

Protein

Organism

Humans

Pharmacological action

Yes

General Function

Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:26919761, PubMed:28126851, PubMed:8768735). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26875626, PubMed:8768735). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (By similarity)

Specific Function

amyloid-beta binding

Gene Name

GRIN2B

Uniprot ID

Q13224

Uniprot Name

Glutamate receptor ionotropic, NMDA 2B

Molecular Weight

166365.885 Da

References

1. Vanover KE, Davis RE, Zhou Y, Ye W, Brasic JR, Gapasin L, Saillard J, Weingart M, Litman RE, Mates S, Wong DF: Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Neuropsychopharmacology. 2019 Feb;44(3):598-605. doi: 10.1038/s41386-018-0251-1. Epub 2018 Oct 26. [Article]

Details3. 5-hydroxytryptamine receptor 2A

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). 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) (PubMed:28129538, PubMed:35084960). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:28129538, PubMed:35084960). HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:28129538, PubMed:35084960). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538, PubMed:35084960). Affects neural activity, perception, cognition and mood (PubMed:18297054). 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 (By similarity)

Specific Function

1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding

Gene Name

HTR2A

Uniprot ID

P28223

Uniprot Name

5-hydroxytryptamine receptor 2A

Molecular Weight

52602.58 Da

References

1. Kumar B, Kuhad A, Kuhad A: Lumateperone: a new treatment approach for neuropsychiatric disorders. Drugs Today (Barc). 2018 Dec;54(12):713-719. doi: 10.1358/dot.2018.54.12.2899443. [Article]
2. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Details4. D(2) dopamine receptor

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Partial agonist

General Function

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity)

Specific Function

dopamine binding

Gene Name

DRD2

Uniprot ID

P14416

Uniprot Name

D(2) dopamine receptor

Molecular Weight

50618.91 Da

References

1. Kumar B, Kuhad A, Kuhad A: Lumateperone: a new treatment approach for neuropsychiatric disorders. Drugs Today (Barc). 2018 Dec;54(12):713-719. doi: 10.1358/dot.2018.54.12.2899443. [Article]

Details5. D(1A) dopamine receptor

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

General Function

Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase

Specific Function

arrestin family protein binding

Gene Name

DRD1

Uniprot ID

P21728

Uniprot Name

D(1A) dopamine receptor

Molecular Weight

49292.765 Da

References

1. Kumar B, Kuhad A, Kuhad A: Lumateperone: a new treatment approach for neuropsychiatric disorders. Drugs Today (Barc). 2018 Dec;54(12):713-719. doi: 10.1358/dot.2018.54.12.2899443. [Article]

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Drug created at November 18, 2007 18:29 / Updated at July 01, 2023 10:08