WAY-100635

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H34N4O2
Molecular Weight	422.5631
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=CC=C1N2CCN(CCN(C(=O)C3CCCCC3)C4=CC=CC=N4)CC2

InChI

InChIKey=SBPRIAGPYFYCRT-UHFFFAOYSA-N

InChI=1S/C25H34N4O2/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

HIDE SMILES / InChI

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 177 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 2849		8.87 null [pIC50]
Dopamine D4 receptor 76 Target ID: CHEMBL219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16915381 \| https://www.ncbi.nlm.nih.gov/pubmed/19179855	Agonist 2752		2.4 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Anxiety 275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8788530	Primary	Preclinical	Unknown Approved Use Unknown
Cognition disorders 26 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10728875	Primary	Preclinical	Unknown Approved Use Unknown
Diabetes mellitus 93 Sources: http://adisinsight.springer.com/drugs/800002783	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
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.	2009-09-15	19410634
Differential effects of M1 and 5-hydroxytryptamine1A receptors on atypical antipsychotic drug-induced dopamine efflux in the medial prefrontal cortex.	2009-09	19491322
The role of the dorsal raphe nucleus in the development, expression, and treatment of L-dopa-induced dyskinesia in hemiparkinsonian rats.	2009-07	19309758
The sigma-1 antagonist BMY-14802 inhibits L-DOPA-induced abnormal involuntary movements by a WAY-100635-sensitive mechanism.	2009-07	19283364
Contribution of the striatum to the effects of 5-HT1A receptor stimulation in L-DOPA-treated hemiparkinsonian rats.	2009-05-15	19115412
Inhibition of monoamine oxidases desensitizes 5-HT1A autoreceptors and allows nicotine to induce a neurochemical and behavioral sensitization.	2009-01-28	19176807
Activation of serotonin 5-HT1-receptors decreased gripping-induced immobility episodes in taiep rats.	2009-01-09	18996171
Involvement of glutamate neurotransmission and N-methyl-d-aspartate receptor in the activation of midbrain dopamine neurons by 5-HT1A receptor agonists: an electrophysiological study in the rat.	2008-10-28	18801415
Stress-induced hyperthermia and basal body temperature are mediated by different 5-HT(1A) receptor populations: a study in SERT knockout rats.	2008-08-20	18606402
Fluoxetine-induced proliferation and differentiation of neural progenitor cells isolated from rat postnatal cerebellum.	2008-08-01	18573488
Delta(9)-tetrahydrocannabinol prolongs the immobility time in the mouse forced swim test: involvement of cannabinoid CB(1) receptor and serotonergic system.	2008-07-28	18565508
Serotonin activates presynaptic and postsynaptic receptors in rat globus pallidus.	2008-04	18234984
Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells.	2008-02-26	18190908
Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model.	2008	18570192
5-HT1A receptors mediate (+)8-OH-DPAT-stimulation of extracellular signal-regulated kinase (MAP kinase) in vivo in rat hypothalamus: time dependence and regional differences.	2007-12-05	17976547
Substance P neurokinin 1 receptor activation within the dorsal raphe nucleus controls serotonin release in the mouse frontal cortex.	2007-12	17890358
3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 5-hydroxytryptamine 1A receptors.	2007-11	17702902
Descending facilitation of spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats.	2007-10	17634400
Distinct electrophysiological effects of paliperidone and risperidone on the firing activity of rat serotonin and norepinephrine neurons.	2007-09	17530476
Effects of repetitive administration of tianeptine, zinc hydroaspartate and electroconvulsive shock on the reactivity of 5-HT(7) receptors in rat hippocampus.	2007-08-26	18195451
Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats.	2007-07	17452372
Antagonist-induced increase in 5-HT1A-receptor expression in adult rat hippocampus and cortex.	2007-07	17447257
Role of peripheral 5-HT1A receptors in detrusor over activity associated with partial bladder outlet obstruction in female rats.	2007-04-30	17320854
Serotonin receptor involvement in effects of restraint on female rat lordosis behavior.	2007-04	17368527
Role of postsynaptic serotonin1A receptors in risperidone-induced increase in acetylcholine release in rat prefrontal cortex.	2007-03-22	17258195
The partial 5-HT(1A) agonist buspirone reduces the expression and development of l-DOPA-induced dyskinesia in rats and improves l-DOPA efficacy.	2007-03-02	17553556
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.	2007-03	17159160
Acetaminophen recruits spinal p42/p44 MAPKs and GH/IGF-1 receptors to produce analgesia via the serotonergic system.	2007-02	17088403
Anticonvulsant effect of the selective 5-HT1B receptor agonist CP 94253 in mice.	2006-07-10	16765343
WAY-100635 antagonist-induced plasticity of 5-HT receptors: regulatory differences between a stable cell line and an in vivo native system.	2006-07	16805803
Early life blockade of 5-hydroxytryptamine 1A receptors normalizes sleep and depression-like behavior in adult knock-out mice lacking the serotonin transporter.	2006-05-17	16707806
MDMA and fenfluramine reduce L-DOPA-induced dyskinesia via indirect 5-HT1A receptor stimulation.	2006-05	16817869
Clozapine modulates aromatic L-amino acid decarboxylase activity in mouse striatum.	2006-05	16415089
Repeated administration of citalopram and imipramine alters the responsiveness of rat hippocampal circuitry to the activation of 5-HT7 receptors.	2005-11-07	16253236
Differential effects of the 5-hydroxytryptamine (5-HT)1A receptor inverse agonists Rec 27/0224 and Rec 27/0074 on electrophysiological responses to 5-HT1A receptor activation in rat dorsal raphe nucleus and hippocampus in vitro.	2005-10	15951403
Inhibition of serotonergic neurons in the nucleus paragigantocellularis lateralis fragments sleep and decreases rapid eye movement sleep in the piglet: implications for sudden infant death syndrome.	2005-09-07	16148240
Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats.	2005-08	15996562
In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors.	2005-07-11	15985260
Serotonin1A-receptor antagonism blocks psychostimulant properties of diethylpropion in marmosets (Callithrix penicillata).	2005-03-21	15777778
Role of 5-HT1A and 5-HT1B receptors in the antinociceptive effect of tramadol.	2005-03-21	15777775
Dopamine uptake inhibitor-induced rotation in 6-hydroxydopamine-lesioned rats involves both D1 and D2 receptors but is modulated through 5-hydroxytryptamine and noradrenaline receptors.	2005-03	15542624
Citalopram combined with WAY 100635 inhibits ejaculation and ejaculation-related Fos immunoreactivity.	2005-02-10	15713429
N-oxide analogs of WAY-100635: new high affinity 5-HT(1A) receptor antagonists.	2005-02-01	15653354
Anticataleptic properties of alpha2 adrenergic antagonists in the crossed leg position and bar tests: differential mediation by 5-HT1A receptor activation.	2005-02	15448976
Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.	2004-12-06	15364487
Cloned human 5-HT1A receptor pharmacology determined using agonist binding and measurement of cAMP accumulation.	2004-10	15482641
WAY100635 and female rat lordosis behavior.	2004-07-09	15193537
Acute treatment with the antidepressant fluoxetine internalizes 5-HT1A autoreceptors and reduces the in vivo binding of the PET radioligand [18F]MPPF in the nucleus raphe dorsalis of rat.	2004-06-09	15190115
Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.	2004-04-30	15145142
The hypotensive effect of BMY 7378 involves central 5-HT1A receptor stimulation in the adult but not in the young rat.	2004-04-02	15631873

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 `Mon Mar 31 17:47:51 GMT 2025` Edited by `admin` on `Mon Mar 31 17:47:51 GMT 2025`
Record UNII	71IH826FEG
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

WAY-100635

Common Name

English

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

Preferred Name

English

Code System Code Type Description

WIKIPEDIA

WAY 100635