FLESINOXAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H26FN3O4
Molecular Weight	415.4579
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC[C@H]1COC2=C(C=CC=C2O1)N3CCN(CCNC(=O)C4=CC=C(F)C=C4)CC3

InChI

InChIKey=NYSDRDDQELAVKP-SFHVURJKSA-N

InChI=1S/C22H26FN3O4/c23-17-6-4-16(5-7-17)22(28)24-8-9-25-10-12-26(13-11-25)19-2-1-3-20-21(19)29-15-18(14-27)30-20/h1-7,18,27H,8-15H2,(H,24,28)/t18-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C22H26FN3O4
Molecular Weight	415.4579
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8263314 | https://www.ncbi.nlm.nih.gov/pubmed/8614706 | https://adisinsight.springer.com/drugs/800001126

FLESINOXAN, a phenylpiperazine derivative, is a selective agonist for 5-HT1A receptors. It is an antidepressant agent which clinical development was stopped.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL273 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9022796	Partial Agonist 290		1.7 nM [Ki]

PubMed

Title	Date	PubMed
Differential cardiovascular effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), flesinoxan, 5-methyl-urapidil and MDL 75,608A in conscious spontaneously hypertensive rats.	1993	7906241
Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.	1998 Aug 21	9760039
HPA axis dysfunction in major depression: relationship to 5-HT(1A) receptor activity.	2001	11490174
Stress-induced hyperthermia in the 5-HT(1A) receptor knockout mouse is normal.	2001 Apr 1	11297713
Flesinoxan, a 5-HT1A receptor agonist/alpha 1-adrenoceptor antagonist, lowers intraocular pressure in NZW rabbits.	2001 Aug	11840354
Corticosterone responses in 5-HT1B receptor knockout mice to stress or 5-HT1A receptor activation are normal.	2001 Feb	11243496
The release of noradrenaline in the locus coeruleus and prefrontal cortex studied with dual-probe microdialysis.	2001 Jul 6	11430860
Generalization of serotonin (5-HT)1A agonists and the antipsychotics, clozapine, ziprasidone and S16924, but not haloperidol, to the discriminative stimuli elicited by PD128,907 and 7-OH-DPAT.	2001 Jun	11378160
Acute and chronic effects of citalopram on postsynaptic 5-hydroxytryptamine(1A) receptor-mediated feedback: a microdialysis study in the amygdala.	2001 Mar	11259482
[Participation of 5-HT1A-receptors in regulating various types of aggressive behavior].	2001 Nov-Dec	11871034
Protective effects of 5-HT1A receptor agonists against emotional changes produced by stress stimuli are related to their neuroendocrine effects.	2001 Oct	11588113
Anxiolytic properties of the selective, non-peptidergic CRF(1) antagonists, CP154,526 and DMP695: a comparison to other classes of anxiolytic agent.	2001 Oct	11557172
5-HT(1B) receptor knockout mice show no adaptive changes in 5-HT(1A) receptor function as measured telemetrically on body temperature and heart rate responses.	2002 Jan 1	11827741
5-HT1A dysfunction in borderline personality disorder.	2002 Jul	12171388
[Effect of (+/-)-pindolol on the central 5-HT1A receptor by the use of in vivo microdialysis and hippocampal slice preparations].	2002 Jun	12166089
Pharmacokinetic-pharmacodynamic modelling of the hypothermic and corticosterone effects of the 5-HT1A receptor agonist flesinoxan.	2002 Jun 7	12065193
Hormonal and temperature responses to the 5-HT1A receptor agonist flesinoxan in normal volunteers.	2002 Oct	12373416
Neuroendocrine evaluation of 5-HT1A function in male alcoholic patients.	2002 Oct	12183221
Psychopharmacology of anxiety disorders.	2002 Sep	22033867
Differential effects of the 5-HT1A receptor agonist flesinoxan given locally or systemically on REM sleep in the rat.	2003 Oct 8	14575796
Effects of repeated testing in two inbred strains on flesinoxan dose-response curves in three mouse models for anxiety.	2004 Jun 21	15194449
Mechanism-based pharmacokinetic-pharmacodynamic modeling of 5-HT1A receptor agonists: estimation of in vivo affinity and intrinsic efficacy on body temperature in rats.	2004 Mar	14718609
Occupancy of agonist drugs at the 5-HT1A receptor.	2004 May	14985704
Effects of the 5-HT1A receptor ligands flesinoxan and WAY 100635 given systemically or microinjected into the laterodorsal tegmental nucleus on REM sleep in the rat.	2004 May 5	15084431
Differential ion current activation by human 5-HT(1A) receptors in Xenopus oocytes: evidence for agonist-directed trafficking of receptor signalling.	2005 Dec	15964603
5-HT1A receptor agonist affects fear conditioning through stimulations of the postsynaptic 5-HT1A receptors in the hippocampus and amygdala.	2006 Feb 17	16460727
Contractile effects of 5-hydroxytryptamine and 5-carboxamidotryptamine in the equine jejunum.	2006 Jan	16230998
SLV313 (1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-4- [5-(4-fluoro-phenyl)-pyridin-3-ylmethyl]-piperazine monohydrochloride): a novel dopamine D2 receptor antagonist and 5-HT1A receptor agonist potential antipsychotic drug.	2007 Jan	16710314
Flesinoxan challenge suggests that chronic treatment with paroxetine in rats does not desensitize receptors controlling 5-HT synthesis.	2008 Dec	18786747
Assessing the neuronal serotonergic target-based antidepressant stratagem: impact of in vivo interaction studies and knockout models.	2008 Sep	19506722
A pilot study of rizatriptan and visually-induced motion sickness in migraineurs.	2009 Aug 6	19680473
Peripheral 5-HT1A and 5-HT7 serotonergic receptors modulate parasympathetic neurotransmission in long-term diabetic rats.	2010	21403818
Modifying 5-HT1A Receptor Gene Expression as a New Target for Antidepressant Therapy.	2010	20661455
Chronic thromboembolic pulmonary hypertension.	2010 Apr	20376164
Rocuronium-induced neuromuscular block after long pretreatment of clonidine in rabbits.	2010 Sep	20877704

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:37:23 GMT 2023` Edited by `admin` on `Fri Dec 15 17:37:23 GMT 2023`
Record UNII	3V574S89E1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLESINOXAN

Official Name

English

flesinoxan [INN]

Common Name

English

FLESINOXAN [MI]

Common Name

English

(+)-(S)-P-FLUORO-N-(2-(4-(2-(HYDROXYMETHYL)-1,4-BENZODIOXAN-5-YL)-1-PIPERAZINYL)ETHYL)BENZAMIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47794