WAY-100635 HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H34N4O2.3ClH
Molecular Weight	531.946
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.Cl.COC1=C(C=CC=C1)N2CCN(CCN(C(=O)C3CCCCC3)C4=NC=CC=C4)CC2

InChI

InChIKey=QDUDBLVWOSYWID-UHFFFAOYSA-N

InChI=1S/C25H34N4O2.3ClH/c1-31-23-12-6-5-11-22(23)28-18-15-27(16-19-28)17-20-29(24-13-7-8-14-26-24)25(30)21-9-3-2-4-10-21;;;/h5-8,11-14,21H,2-4,9-10,15-20H2,1H3;3*1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C25H34N4O2
Molecular Weight	422.5631
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800002783
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16915381 | https://www.ncbi.nlm.nih.gov/pubmed/8566121 | https://www.ncbi.nlm.nih.gov/pubmed/8768719 | http://link.springer.com/chapter/10.1007%2F978-94-011-0429-6_9

WAY-100635 is an achiral phenylpiperazine derivative that originally discovered as an antagotist of 5-HT1A receptor. Later WAY-100635 was described as a potent dopamine D4 receptor agonist. WAY-100635 was in preclinical studies for the treatment of Diabetes mellitus, Anxiety and Cognition disorders, howevere the development was discontinued. Isotope labeled WAY-100635 could be used for the study of central 5-HT 1A receptors with potential for application to the study of neuropsychiatric disorders and to the human pharmacology of psychoactive drugs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8566121 \| https://www.ncbi.nlm.nih.gov/pubmed/10962248 \| https://www.ncbi.nlm.nih.gov/pubmed/8768719 \| https://www.ncbi.nlm.nih.gov/pubmed/9504386 \| https://www.ncbi.nlm.nih.gov/pubmed/8788530 \| https://www.ncbi.nlm.nih.gov/pubmed/16805803	Antagonist 2778		8.87 null [pIC50]
Dopamine D4 receptor 71 Target ID: CHEMBL219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16915381 \| https://www.ncbi.nlm.nih.gov/pubmed/19179855	Agonist 2678		2.4 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8788530	Primary	Preclinical	Unknown Approved Use Unknown
Cognition disorders 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10728875	Primary	Preclinical	Unknown Approved Use Unknown
Diabetes mellitus 91 Sources: http://adisinsight.springer.com/drugs/800002783	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
S 15535, a benzodioxopiperazine acting as presynaptic agonist and postsynaptic 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine.	1999 Nov	10578133
Involvement of 5-hydroxytryptamine(1A) receptors in nicotine-induced tail tremor in rats.	2000 Nov 10	11070179
Effects of the serotonin 5-HT(2) antagonist, ritanserin, and the serotonin 5-HT(1A) antagonist, WAY 100635, on cocaine-seeking in rats.	2000 Oct	11124402
Endogenous 5-HT tonically inhibits spontaneous firing activity of dorsal hippocampus CA1 pyramidal neurons through stimulation of 5-HT(1A) receptors in quiet awake rats: in vivo electrophysiological evidence.	2001 Feb	11120396
Catalepsy induced by the 5-HT(1A) receptor antagonist WAY 100635 in rats pretreated with the selective serotonin reuptake inhibitor citalopram.	2001 Jan 12	11164384
Involvement of somatodendritic 5-HT(1A) receptors in Delta(9)-tetrahydrocannabinol-induced hypothermia in the rat.	2001 Jul-Aug	11509221
Biochemical, electrophysiological and neurohormonal studies with B-20991, a selective 5-HT1A receptor agonist.	2001 May	11360001
5-HT1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential.	2001 May 25	11408031
Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models.	2001 Nov 27	11723272
5-HT receptor subtypes involved in the spinal antinociceptive effect of acetaminophen in rats.	2001 Nov 30	11734181
5-HT1A agonist/antagonist modification of cocaine stimulant effects: implications for cocaine mechanisms.	2002 Apr 15	11853856
5-HT7 receptors modulate synchronized network activity in rat hippocampus.	2002 Jan	11750918
5-HT1A receptor-mediated regulation of mitogen-activated protein kinase phosphorylation in rat brain.	2002 Oct 4	12354565
Repeated administration of milnacipran induces rapid desensitization of somatodendritic 5-HT1A autoreceptors but not postsynaptic 5-HT1A receptors.	2002 Sep	12236634
Pharmacological characterization of MP349, a novel 5-HT1A-receptor antagonist with anxiolytic-like activity, in mice and rats.	2003 Apr	12803776
Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat.	2003 Feb	12589378
Involvement of presynaptic 5-HT(1A) and benzodiazepine receptors in the anticonflict activity of 5-HT(1A) receptor antagonists.	2003 Jun 13	12809949
Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats.	2004 Apr 12	15087245
Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.	2004 Dec 6	15364487
Dissociation of rewarding and dopamine transporter-mediated properties of amphetamine.	2004 May 18	15136721
Combined treatment of quetiapine with haloperidol in animal models of antipsychotic effect and extrapyramidal side effects: comparison with risperidone and chlorpromazine.	2004 Oct	15083255
Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats.	2005 Aug	15996562
Anticataleptic properties of alpha2 adrenergic antagonists in the crossed leg position and bar tests: differential mediation by 5-HT1A receptor activation.	2005 Feb	15448976
N-oxide analogs of WAY-100635: new high affinity 5-HT(1A) receptor antagonists.	2005 Feb 1	15653354
Citalopram combined with WAY 100635 inhibits ejaculation and ejaculation-related Fos immunoreactivity.	2005 Feb 10	15713429
Role of peripheral 5-HT1A receptors in detrusor over activity associated with partial bladder outlet obstruction in female rats.	2007 Apr 30	17320854
Single exposure to a serotonin 1A receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin, produces a prolonged heterologous desensitization of serotonin 2A receptors in neuroendocrine neurons in vivo.	2007 Mar	17159160
Role of postsynaptic serotonin1A receptors in risperidone-induced increase in acetylcholine release in rat prefrontal cortex.	2007 Mar 22	17258195
Descending facilitation of spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats.	2007 Oct	17634400
Fluoxetine-induced proliferation and differentiation of neural progenitor cells isolated from rat postnatal cerebellum.	2008 Aug 1	18573488
Differential effects of M1 and 5-hydroxytryptamine1A receptors on atypical antipsychotic drug-induced dopamine efflux in the medial prefrontal cortex.	2009 Sep	19491322
The firing activity of pyramidal neurons in medial prefrontal cortex and their response to 5-hydroxytryptamine-1A receptor stimulation in a rat model of Parkinson's disease.	2009 Sep 15	19410634

Patents

Sample Use Guides

In Vivo Use Guide

mice: 3.0 mg/kg, i.p. rats: 200 ng, injected in the median raphé nucleus cats: 0.025-0.5 mg/kg i.v.

Route of Administration: Other

In Vitro Use Guide

Exposure of h5-HT(1A) CHO cells to WAY-100635 decreased the cell-surface h5-HT(1A) receptor density in a way that was both time (24-72 h) and concentration (1-100 nM) dependent. In dorsal raphe nucleus slices superfused with WAY 100635 (10 nM), the majority of putative 5-HT neurons increased their firing rate. In addition, WAY 100635 completely prevented the decrease in firing rate produced by 5-HT (3-15 microM), 8-OH-DPAT (10 nM), 5-carboxamidotryptamine (20 nM) and lesopitron (100 nM).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:12:11 GMT 2023` Edited by `admin` on `Fri Dec 15 18:12:11 GMT 2023`
Record UNII	8S48P899NE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

WAY-100635 HYDROCHLORIDE

Common Name

English

WAY-100635 TRIHYDROCHLORIDE

Code

English

CYCLOHEXANECARBOXAMIDE, N-(2-(4-(2-METHOXYPHENYL)-1-PIPERAZINYL)ETHYL)-N-2-PYRIDINYL-, TRIHYDROCHLORIDE

Common Name

English

WAY 100635 HYDROCHLORIDE

Code

English

Code System Code Type Description

PUBCHEM

104911