FLUPERLAPINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20FN3
Molecular Weight	309.3806
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CC1)C2=NC3=C(CC4=C2C=CC=C4)C=CC(F)=C3

InChI

InChIKey=OBWGMKKHCLHVIE-UHFFFAOYSA-N

InChI=1S/C19H20FN3/c1-22-8-10-23(11-9-22)19-17-5-3-2-4-14(17)12-15-6-7-16(20)13-18(15)21-19/h2-7,13H,8-12H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6728910 | https://www.ncbi.nlm.nih.gov/pubmed/6149595 | http://adisinsight.springer.com/drugs/800000549 | https://www.ncbi.nlm.nih.gov/pubmed/10681368

Fluperlapine is dibenzazepine chemically and pharmacologically similar to clozapine. Fluperlapine had no cataleptogenic effect and did not inhibit the apomorphine- and d-amphetamine-induced stereotypes. Fluperlapine is fairly effective neuroleptic drug with a fast-acting antipsychotic affect. The effects in movement disorders imply that fluperlapine is less liable than traditional neuroleptics to induce acute extrapyramidal side effects and tardive dyskinesia and is particularly beneficial in the treatment of patients vulnerable to neurological side-effects. It was demonstrated efficacy in the treatment of a variety of medical conditions including schizophrenia, psychosis associated with Parkinson's disease and dystonia. It has the capacity for producing life-threatening agranulocytosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL339 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8101877	Binding Agent 1064	13.3 µM [Ki]
Dopamine D1 receptor 101 Target ID: CHEMBL265 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8101877	Binding Agent 1064	14.1 µM [Ki]
Serotonin 2 (5-HT2) receptor 87 Target ID: CHEMBL2093870 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8101877	Binding Agent 1064	0.38 µM [Ki]
Serotonin 6 (5-HT6) receptor 45 Target ID: CHEMBL3372 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7908055	Binding Agent 1064	7.8 null [pKi]
Serotonin 7 (5-HT7) receptor 31 Target ID: CHEMBL3223 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7908055	Binding Agent 1064	8.3 null [pKi]
Serotonin 2c (5-HT2c) receptor 124 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10991983	Inverse Agonist 80	56.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6145426 https://www.ncbi.nlm.nih.gov/pubmed/6148712	Primary		Phase II 1132	Unknown Approved Use Unknown
Hyperkinesia 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6149595	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP19A1 60	FMO 35 CYPs 33

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144205333	inconclusive [IC50 18.3564 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466413	inconclusive [IC50 27.5404 uM]
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144205333	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466413	no
CYP3A4 1925	inducer 1573 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144205333	yes [Activation 25.1189 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/1545398/	yes [Ki 3.7 uM]

Drug as victim

Target	Modality	Activity
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/1545398/	yes
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/2322314/	yes
FMO 35	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/2322314/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144205333

Sourcing

Vendor/Aggregator	ID	URL
BOC Sciences	67121-76-0	http://www.bocsci.com/description.asp?cas=67121-76-0
Compound Cloud	49381
HongKong Chemhere	SCE25934
MuseChem	I012630	https://www.musechem.com/product/I012630.html
Tetrahedron	TS60819	http://www.thsci.com/search.do?q=TS60819
eMolecules	1933744	https://orderbb.emolecules.com/search/#?query=1933744

PubMed

Title	Date	PubMed
Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine.	1985	2864254
Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.	1996 Jan	8522988
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.	2005 May	15821958

Patents

Sample Use Guides

In Vivo Use Guide

300 mg per day during 28-days

Route of Administration: Oral

In Vitro Use Guide

Atypical neuroleptic fluperlapine showed inhibition on forskolin-induced accumulation of [3H]cAMP on the human muscarinic m4 receptors expressed in CHO cells with EC50=600 nM.

Name

Type

Language

FLUPERLAPINE

Official Name

English

FLUPERLAPINE [MART.]

Common Name

English

fluperlapine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66885