U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C11H12N2O2.ClH
Molecular Weight 240.686
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IDAZOXAN HYDROCHLORIDE, (S)-

SMILES

Cl.C1CN=C(N1)[C@H]2COC3=CC=CC=C3O2

InChI

InChIKey=MYUBYOVCLMEAOH-HNCPQSOCSA-N
InChI=1S/C11H12N2O2.ClH/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);1H/t10-;/m1./s1

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 C11H12N2O2
Molecular Weight 204.2252
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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. Idazoxan`s diastereoisomers possess different relative selectivity for alpha2- pre- and postsynaptic receptors: ( )-idazoxan was 7-8 times more potent than (-)-idazoxan in inhibiting p-[3H]aminoclonidine binding, and 40 times more active in antagonizing clonidine at presynaptic level, indicating a better selectivity for alpha2-presynaptic sites. The pre- and postsynaptic alpha2-adrenoceptors have a different affinity for the two enantiomers of idazoxan. Although the stereoisomers are closely related structurally, ( )-idazoxan possesses a stronger affinity for presynaptic sites. This stereoselectivity was less evident for postsynaptic sites. In rats and dogs, both enantiomers antagonized the sympathoinhibitory effects of clonidine. In rats, ( )- idazoxan was 4-7 times more potent than (-)- idazoxan and 3-8 times more than (-)- idazoxan in dogs. A same order of potency was observed against the sedative effects of clonidine and azepexole in chicks, ( )- idazoxan being 8 times more potent than (-)- idazoxan. Although ( )- idazoxan was more potent than (-) idazoxan, binding studies revealed (-)- idazoxan to be more selective than ( )- idazoxan at central sites. It is concluded that ( )- idazoxan antagonizes both alpha-1 and alpha-2 adrenoceptors and (-)- idazoxan is selective for alpha-2 adrenoceptors. ( )- idazoxan is equipotent for antagonizing postsynaptic alpha-I and alpha-2 adrenoceptors. It is also a potent alpha-2 antagonist at presynaptic and central sites and is 4-8 times more potent than (-)- idazoxan but less selective.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7.2 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
(S)-IDAZOXAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
27 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
(S)-IDAZOXAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.8 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
(S)-IDAZOXAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
(Imidazolinyl-2)-2-benzodioxane 1-4 (idazoxan) and its stereoisomers, new alpha 2-antagonists.
1985
Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists.
1986 Oct
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: I.V. route: in rats each enantiomer of idazoxan (( )-idazoxan and (-)-idazoxan) was injected i.v. in cumulative doses (0.01-10 mg/kg) after stabilization of blood pressure and heart rats. Injections were performed every 2 min. https://www.ncbi.nlm.nih.gov/pubmed/2873908
Young healthy male subjects were allocated at random to receive a single dose of each of the following substances on one occasion: 20 mg of idazoxan racemate (polymorph of form I); 10 mg of the R(−) enantiomer; 10 mg of the S( ) enantiomer.
Route of Administration: Oral
In Vitro Use Guide
Binding studies were performed on rat hypothalamic and cortical membranes with p-[3H]aminoclonidine as a selective alpha2-adrenoceptor radioligand. The specific binding of p-[3H]aminoclonidine (2.5 nM) was examined in the presence of increasing concentrations (from 0.03 nM to 1 uM) of idazoxan stereoisomers. (+)-idazoxan (Ki = 2.4 nM) was 7-8 times more potent than (-)- idazoxan (Ki= 18.7 nM) in inhibiting postsynaptic alpha2-adrenoceptors. Competition binding experiments with the two enantiomers were also performed on alpha1-adrenoceptors using [3H]WB4101 as radioligand ((+)-idazoxan Ki=275 nM; (-)-idazoxan Ki =425 nM).
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:23:53 UTC 2023
Edited
by admin
on Sat Dec 16 09:23:53 UTC 2023
Record UNII
DUA4F30QF8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IDAZOXAN HYDROCHLORIDE, (S)-
Common Name English
1H-IMIDAZOLE, 2-((2S)-2,3-DIHYDRO-1,4-BENZODIOXIN-2-YL)-4,5-DIHYDRO-, MONOHYDROCHLORIDE
Systematic Name English
1H-IMIDAZOLE, 2-(2,3-DIHYDRO-1,4-BENZODIOXIN-2-YL)-4,5-DIHYDRO-, MONOHYDROCHLORIDE, (S)-
Common Name English
2-(2,3-DIHYDRO-1,4-BENZODIOXIN-2-YL)-4,5-DIHYDRO-1H-IMIDAZOLE HYDROCHLORIDE, (S)-
Systematic Name English
Code System Code Type Description
PUBCHEM
72941621
Created by admin on Sat Dec 16 09:23:53 UTC 2023 , Edited by admin on Sat Dec 16 09:23:53 UTC 2023
PRIMARY
CAS
89141-62-8
Created by admin on Sat Dec 16 09:23:53 UTC 2023 , Edited by admin on Sat Dec 16 09:23:53 UTC 2023
PRIMARY
FDA UNII
DUA4F30QF8
Created by admin on Sat Dec 16 09:23:53 UTC 2023 , Edited by admin on Sat Dec 16 09:23:53 UTC 2023
PRIMARY
Related Record Type Details
RACEMATE -> ENANTIOMER