| Stereochemistry | ABSOLUTE |
| Molecular Formula | C11H12N2O2 |
| Molecular Weight | 204.2252 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C1CN=C(N1)[C@H]2COC3=C(O2)C=CC=C3
InChI
InChIKey=HPMRFMKYPGXPEP-SNVBAGLBSA-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)/t10-/m1/s1
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.
CNS Activity
Originator
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
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
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 RECORD
