IDAZOXAN

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H12N2O2
Molecular Weight	204.2252
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CN=C(N1)C2COC3=CC=CC=C3O2

InChI

InChIKey=HPMRFMKYPGXPEP-UHFFFAOYSA-N

InChI=1S/C11H12N2O2/c1-2-4-9-8(3-1)14-7-10(15-9)11-12-5-6-13-11/h1-4,10H,5-7H2,(H,12,13)

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800000691 | https://www.ncbi.nlm.nih.gov/pubmed/2875218

Idazoxan is an alpha2 receptor antagonist which also shows activity at imidazoline I1 and I2 receptors and modulates the release of dopamine. Idazoxan was in phase II development in the US. Later the development of idazoxan for schizophrenia was discontinued. It was also in clinical trials for cognition disorders in United Kingdom, and was also discontinued. Idazoxan is used in scientific research as a tool for the study of alpha 2-adrenoceptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Alpha-2b adrenergic receptor 27 Target ID: CHEMBL1942 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10636247	Antagonist 2778	7.71 null [pIC50]
Alpha-2a adrenergic receptor 63 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10636247	Antagonist 2778	8.08 null [pIC50]
Alpha-2c adrenergic receptor 37 Target ID: CHEMBL1916 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10636247	Antagonist 2778	7.27 null [pIC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: http://adisinsight.springer.com/drugs/800000691 https://www.ncbi.nlm.nih.gov/pubmed/8733795	Primary		Phase II 1132	Unknown Approved Use Unknown
Major depressive disorder 173 Sources: https://clinicaltrials.gov/ct2/show/NCT00294944 http://adisinsight.springer.com/drugs/800000691	Primary		Phase III 656	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
179.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2872058/	0.3 mg/kg single, oral dose: 0.3 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		IDAZOXAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
560.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2872058/	0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		IDAZOXAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.59 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2872058/	0.3 mg/kg single, oral dose: 0.3 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		IDAZOXAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2872058/	0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		IDAZOXAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

PubMed

Title	Date	PubMed
A morpholinocatechol compound (UK42620) with clonidine- and tyramine-like actions.	2001 Aug	11952871
Differential responses of regional vascular beds to local injection of agmatine in rats.	2001 Dec	11930224
Combined alpha 2-adrenergic/D2 dopamine receptor blockade fails to reproduce the ability of clozapine to reverse phencyclidine-induced deficits in prepulse inhibition of startle.	2001 Dec	11797077
In vitro and in vivo impairment of alpha2-adrenergic receptor-dependent antilipolysis by fatty acids in human adipose tissue.	2001 Dec	11753754
Functional and pharmacological characterization of the modulatory role of serotonin on the firing activity of locus coeruleus norepinephrine neurons.	2001 Dec 13	11730697
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine. II. Electrophysiological and fluorimetric studies.	2001 Dec 15	11755123
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine. I. Secretory and morphological studies.	2001 Dec 15	11755122
Down-regulation of MAO-B activity and imidazoline receptors in rat brain following chronic treatment of morphine.	2001 Jul	11749830
Agmatine inhibits carotid sinus baroreflex in anesthetized rats.	2001 Mar	11742575
Hemodynamic effects of agmatine in Dahl salt-sensitive hypertensive and Dahl salt-resistant rats.	2001 Oct	11833418
The involvement of alpha2-adrenoceptors in the anticonvulsive effect of swim stress in mice.	2001 Oct	11685388
Alpha2-adrenoceptor activation increases a cationic conductance and spontaneous GABAergic synaptic activity in dopaminergic neurones of the rat substantia nigra.	2002	12453479
Changes of the excitability of rat trigeminal root ganglion neurons evoked by alpha(2)-adrenoreceptors.	2002	12435412
Interactions between cutaneous afferent inputs to a withdrawal reflex in the decerebrated rabbit and their control by descending and segmental systems.	2002	12074898
Intrathecal clonidine decreases spinal nitric oxide release in a rat model of complete Freund's adjuvant induced inflammatory pain.	2002 Aug	12184629
Enhanced stability of wild-type and constitutively active alpha(2A)-adrenoceptors by ligands with agonist, silent and inverse agonist properties.	2002 Aug	12122500
Distribution of [(3)H]BU224, a selective imidazoline I(2) binding site ligand, in rat brain.	2002 Aug 16	12176109
Different roles for Gi and Go proteins in modulation of adenylyl cyclase type-2 activity.	2002 Dec	12472880
Agmatine inhibits arginine vasopressin-stimulated urea transport in the rat inner medullary collecting duct.	2002 Dec	12427134
Comparison of the ORL1 receptor-mediated inhibition of noradrenaline release in human and rat neocortical slices.	2002 Feb	11834628
Mechanisms involved in the water intake-related pressor response in the rat.	2002 Feb	11821715
Seasonal changes in the densities of alpha(2) noradrenergic receptors are inversely related to changes in testosterone and the volumes of song control nuclei in male European starlings.	2002 Feb 25	11835182
Testosterone dependence of salt-induced hypertension in Sabra rats and role of renal alpha(2)-adrenoceptor subtypes.	2002 Jan	11752095
Agmatine: a mastoparan-like activity related to direct activation of heterotrimeric G proteins.	2002 Jan 18	11790374
Alpha2-adrenoreceptors profile modulation and high antinociceptive activity of (S)-(-)-2-[1-(biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole.	2002 Jan 3	11754577
Tonic immobility in guinea pigs: a behavioural response for detecting an anxiolytic-like effect?	2002 Jul	12218506
Actions of alpha-2 noradrenergic agonists on spatial working memory and blood pressure in rhesus monkeys appear to be mediated by the same receptor subtype.	2002 Jul	12122489
Effect of antisense knock-down of alpha(2a)- and alpha(2c)-adrenoceptors on the antinociceptive action of clonidine on trigeminal nociception in the rat.	2002 Jul	12098614
Prenatal cocaine exposure alters sensitivity to the effects of idazoxan in a distraction task.	2002 Jul 18	12110452
Characterization of [(3)H]idazoxan binding sites on human platelets.	2002 Jun	12189026
Inhibition of pilocarpine-induced salivation in rats by central noradrenaline.	2002 Jun	12102758
Imidazoline(2) (I(2)) binding site- and alpha(2)-adrenoceptor-mediated modulation of central noradrenergic and HPA axis function in control rats and chronically stressed rats with adjuvant-induced arthritis.	2002 Jun	12069906
Pre- and postjunctional alpha(2)-adrenergic receptors in fetal and adult ovine cerebral arteries.	2002 Jun	12010747
Different alpha-adrenoceptors mediate migration of vascular smooth muscle cells and adventitial fibroblasts in vitro.	2002 Jun	12003847
alpha(2)-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats.	2002 Jun	12003844
Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine.	2002 Jun 12	12079683
Imidazoline drugs stabilize lysosomes and inhibit oxidative cytotoxicity in astrocytes.	2002 Mar 1	11864779
Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain.	2002 May	12031785
Role of histamine H3 receptors in control of mouse intestinal motility in vivo and in vitro: comparison with alpha2-adrenoceptors.	2002 May	12018901
alpha(2B)-Adrenergic receptors activate MAPK and modulate proliferation of primary cultured proximal tubule cells.	2002 May	11934705
In vivo tonic modulation of the noradrenaline release in the rat cortex by locus coeruleus somatodendritic alpha(2)-adrenoceptors.	2002 May 10	12065075
Biochemical and functional characterization of alpha-adrenergic receptors in the rabbit vagina.	2002 Nov 1	12377271
Central serotonergic and adrenergic/imidazoline inhibitory mechanisms on sodium and water intake.	2002 Nov 22	12426052
Adrenoceptors in avian and fish pigment cells.	2002 Oct	12355228
Alpha(1)-adrenoceptor stimulation directly induces growth of vascular wall in vivo.	2002 Oct	12234812
Effects of medullary alpha2-adrenoceptor blockade in the rat.	2002 Oct 25	12398917
Effects of serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibition plus 5-HT(2A) receptor antagonism on the firing activity of norepinephrine neurons.	2002 Sep	12183655
RX 821002 as a tool for physiological investigation of alpha(2)-adrenoceptors.	2002 Summer	12177687
Involvement of I(1)-imidazoline receptors in baroreceptor reflex in the caudal ventrolateral medulla of rats.	2003 Jan 17	12505653
Central alpha(2) adrenergic receptors and cholinergic-induced salivation in rats.	2003 Jan 30	12507689

Patents

Sample Use Guides

In Vivo Use Guide

Parkinson's disease:single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan

Route of Administration: Oral

In Vitro Use Guide

Idazoxan (10(-4) mol/L), an alpha 2-adrenergic receptor (alpha 2-AR) and imidazoline receptor (IR) antagonist, abolished the Agm-induced vasorelaxation completely under the condition of CaCl2-induced precontraction in the isolated aortic artery of rats..

Name

Type

Language

IDAZOXAN

Official Name

English

IDAZOXAN [MI]

Common Name

English

DL-IDAZOXAN

Common Name

English

NSC-759867

Code

English

RACEMIC IDAZOXAN

Common Name

English

2-(2,3-DIHYDRO-1,4-BENZODIOXIN-2-YL)-4,5-DIHYDRO-1H-IMIDAZOLE

Systematic Name

English

idazoxan [INN]

Common Name

English

1H-IMIDAZOLE, 2-(2,3-DIHYDRO-1,4-BENZODIOXIN-2-YL)-4,5-DIHYDRO-

Systematic Name

English

2-IMIDAZOLINE, 2-(1,4-BENZODIOXAN-2-YL)-

Systematic Name

English

(±)-2-(1,4-BENZODIOXAN-2-YL)-2-IMIDAZOLINE

Systematic Name

English

(±)-IDAZOXAN

Common Name

English

Code System Code Type Description

INN

5337