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Idazoxan

January 01, 1970

Idazoxan (INN) is a drug which is used in scientific research. It acts as both a selective α2 adrenergic receptor antagonist, and an antagonist for the imidazoline receptor.[1][2][3][4] Idazoxan has been under investigation as an antidepressant, but it did not reach the market as such. More recently, it is under investigation as an adjunctive treatment in schizophrenia. Due to its α2 receptor antagonism it is capable of enhancing therapeutic effects of antipsychotics, possibly by enhancing dopamine neurotransmission in the prefrontal cortex of the brain, a brain area thought to be involved in the pathogenesis of schizophrenia.

Idazoxan
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • (±)-2-(2,3-dihydro-1,4-benzodioxin-2-yl)-4,5-dihydro-1H-imidazole
CAS Number
  • 79944-58-4 Y
PubChem CID
  • 54459
ChemSpider
  • 49184 N
UNII
  • Y310PA316B
ChEMBL
  • ChEMBL10316 N
CompTox Dashboard (EPA)
  • DTXSID6045161
Chemical and physical data
FormulaC11H12N2O2
Molar mass204.229 g·mol−1
3D model (JSmol)
  • Interactive image
ChiralityRacemic mixture
  • C1CN=C(N1)C2COC3=CC=CC=C3O2
  • 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) N
  • Key:HPMRFMKYPGXPEP-UHFFFAOYSA-N N
 NY (what is this?)  (verify)

Alzheimer's research edit

Mice treated with idazoxan, which blocks the α2A receptor which regulates norepinephrine, behaved similarly to control animals despite still having amyloid-beta plaques in the brain, as a proof-of-concept experiment that dramatically reduced Alzheimer's pathology and symptoms in two mouse models, potentially offering an immediate treatment for this devastating disease.[5]

Synthesis edit

Note that the literature method claims that the old original patented procedure gives a different reaction product formed through a rearrangement.

 
Synthesis:[6][7][8] Old Patent:[9] New Patent:[10]

The reaction of catechol (1) with 2-Chloroacrylonitrile [920-37-6] (2) gives 2-cyano-1,4-benzodioxan [1008-92-0] (3). Pinner reaction with alcoholic hydrogen chloride leads to the iminoether,[11] (4). Treatment with ethylenediamine [107-15-3] (5) gives the imidazoline ring affording Idazoxin (6).

See also edit

References edit

  1. ^ Bousquet P, Bruban V, Schann S, Greney H, Ehrhardt JD, Dontenwill M, Feldman J (June 1999). "Participation of imidazoline receptors and alpha(2-)-adrenoceptors in the central hypotensive effects of imidazoline-like drugs". Annals of the New York Academy of Sciences. 881 (1): 272–8. Bibcode:1999NYASA.881..272B. doi:10.1111/j.1749-6632.1999.tb09369.x. PMID 10415925. S2CID 38772290.
  2. ^ Clarke RW, Harris J (2002). "RX 821002 as a tool for physiological investigation of alpha(2)-adrenoceptors". CNS Drug Reviews. 8 (2): 177–92. doi:10.1111/j.1527-3458.2002.tb00222.x. PMC 6741674. PMID 12177687.
  3. ^ Yakubu MA, Hamilton CA, Howie CA, Reid JL (1988). "Idazoxan and brain alpha2-adrenoceptor in the rabbit". Brain Research. 436: 289–296. doi:10.1016/0006-8993(88)90402-7. PMID 2848612.
  4. ^ Hamilton CA, Yakubu MA, Jardine E, Reid JL (1991). "Imidazole binding sites in rabbit kidney and forebrain membranes". J Auton Pharmacol. 11 (4): 277–83. doi:10.1111/j.1474-8673.1991.tb00325.x. PMID 1939285.
  5. ^ Zhang F, Gannon M, Chen Y, Yan S, Zhang S, Feng W, et al. (January 2020). "β-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3β/tau cascade". Science Translational Medicine. 12 (526). doi:10.1126/scitranslmed.aay6931. PMC 7891768. PMID 31941827.
  6. ^ Chapleo CB, Myers PL (January 1981). "2-[2-(1, 4-benzodioxanyl)]-2-imidazoline hydrochloride". Tetrahedron Letters. 22 (48): 4839–4842. doi:10.1016/S0040-4039(01)92358-5.
  7. ^ Chapleo CB, Davis JA, Myers PL, Readhead MJ, Stillings MR, Welbourn AP, Hampson FC, Sugden K (January 1984). "An investigation of some base induced transformations of the 1, 4‐benzodioxan ring system". Journal of Heterocyclic Chemistry. 21 (1): 77–80. doi:10.1002/jhet.5570210117.
  8. ^ Chapleo CB, Myers PL, Butler RC, Doxey JC, Roach AG, Smith CF (June 1983). "alpha-adrenoreceptor reagents. 1. Synthesis of some 1,4-benzodioxans as selective presynaptic alpha 2-adrenoreceptor antagonists and potential antidepressants". Journal of Medicinal Chemistry. 26 (6): 823–31. doi:10.1021/jm00360a008. PMID 6133953.
  9. ^ US 2979511, Krapcho J, Lott WA, "Certain 1, 4-benzodioxanyl imidazolines and corresponding pyrimidines and process", issued 11 April 1961, assigned to Olin Corp. 
  10. ^ US 7338970, Bougaret J, Avan JL, Segonds R, "Pharmaceutical composition based on idazoxan, salts, hydrates or polymorphs thereof", issued 3 March 2008, assigned to Pierre Fabre Medicament. 
  11. ^ "2,3-Dihydro-1,4-benzodioxin-2-carbimidic acid ethyl ester". PubChem. U.S. National Library of Medicine. CID:10035919.


 

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January 01, 1970
idazoxan, drug, which, used, scientific, research, acts, both, selective, adrenergic, receptor, antagonist, antagonist, imidazoline, receptor, been, under, investigation, antidepressant, reach, market, such, more, recently, under, investigation, adjunctive, tr. Idazoxan INN is a drug which is used in scientific research It acts as both a selective a2 adrenergic receptor antagonist and an antagonist for the imidazoline receptor 1 2 3 4 Idazoxan has been under investigation as an antidepressant but it did not reach the market as such More recently it is under investigation as an adjunctive treatment in schizophrenia Due to its a2 receptor antagonism it is capable of enhancing therapeutic effects of antipsychotics possibly by enhancing dopamine neurotransmission in the prefrontal cortex of the brain a brain area thought to be involved in the pathogenesis of schizophrenia IdazoxanClinical dataRoutes ofadministrationOralATC codenoneLegal statusLegal statusIn general uncontrolledIdentifiersIUPAC name 2 2 3 dihydro 1 4 benzodioxin 2 yl 4 5 dihydro 1H imidazoleCAS Number79944 58 4 YPubChem CID54459ChemSpider49184 NUNIIY310PA316BChEMBLChEMBL10316 NCompTox Dashboard EPA DTXSID6045161Chemical and physical dataFormulaC 11H 12N 2O 2Molar mass204 229 g mol 13D model JSmol Interactive imageChiralityRacemic mixtureSMILES C1CN C N1 C2COC3 CC CC C3O2InChI 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 NKey HPMRFMKYPGXPEP UHFFFAOYSA N N N Y what is this verify Contents 1 Alzheimer s research 2 Synthesis 3 See also 4 ReferencesAlzheimer s research editMice treated with idazoxan which blocks the a2A receptor which regulates norepinephrine behaved similarly to control animals despite still having amyloid beta plaques in the brain as a proof of concept experiment that dramatically reduced Alzheimer s pathology and symptoms in two mouse models potentially offering an immediate treatment for this devastating disease 5 Synthesis editNote that the literature method claims that the old original patented procedure gives a different reaction product formed through a rearrangement nbsp Synthesis 6 7 8 Old Patent 9 New Patent 10 The reaction of catechol 1 with 2 Chloroacrylonitrile 920 37 6 2 gives 2 cyano 1 4 benzodioxan 1008 92 0 3 Pinner reaction with alcoholic hydrogen chloride leads to the iminoether 11 4 Treatment with ethylenediamine 107 15 3 5 gives the imidazoline ring affording Idazoxin 6 See also editImiloxan Efaroxan FluparoxanReferences edit Bousquet P Bruban V Schann S Greney H Ehrhardt JD Dontenwill M Feldman J June 1999 Participation of imidazoline receptors and alpha 2 adrenoceptors in the central hypotensive effects of imidazoline like drugs Annals of the New York Academy of Sciences 881 1 272 8 Bibcode 1999NYASA 881 272B doi 10 1111 j 1749 6632 1999 tb09369 x PMID 10415925 S2CID 38772290 Clarke RW Harris J 2002 RX 821002 as a tool for physiological investigation of alpha 2 adrenoceptors CNS Drug Reviews 8 2 177 92 doi 10 1111 j 1527 3458 2002 tb00222 x PMC 6741674 PMID 12177687 Yakubu MA Hamilton CA Howie CA Reid JL 1988 Idazoxan and brain alpha2 adrenoceptor in the rabbit Brain Research 436 289 296 doi 10 1016 0006 8993 88 90402 7 PMID 2848612 Hamilton CA Yakubu MA Jardine E Reid JL 1991 Imidazole binding sites in rabbit kidney and forebrain membranes J Auton Pharmacol 11 4 277 83 doi 10 1111 j 1474 8673 1991 tb00325 x PMID 1939285 Zhang F Gannon M Chen Y Yan S Zhang S Feng W et al January 2020 b amyloid redirects norepinephrine signaling to activate the pathogenic GSK3b tau cascade Science Translational Medicine 12 526 doi 10 1126 scitranslmed aay6931 PMC 7891768 PMID 31941827 Chapleo CB Myers PL January 1981 2 2 1 4 benzodioxanyl 2 imidazoline hydrochloride Tetrahedron Letters 22 48 4839 4842 doi 10 1016 S0040 4039 01 92358 5 Chapleo CB Davis JA Myers PL Readhead MJ Stillings MR Welbourn AP Hampson FC Sugden K January 1984 An investigation of some base induced transformations of the 1 4 benzodioxan ring system Journal of Heterocyclic Chemistry 21 1 77 80 doi 10 1002 jhet 5570210117 Chapleo CB Myers PL Butler RC Doxey JC Roach AG Smith CF June 1983 alpha adrenoreceptor reagents 1 Synthesis of some 1 4 benzodioxans as selective presynaptic alpha 2 adrenoreceptor antagonists and potential antidepressants Journal of Medicinal Chemistry 26 6 823 31 doi 10 1021 jm00360a008 PMID 6133953 US 2979511 Krapcho J Lott WA Certain 1 4 benzodioxanyl imidazolines and corresponding pyrimidines and process issued 11 April 1961 assigned to Olin Corp US 7338970 Bougaret J Avan JL Segonds R Pharmaceutical composition based on idazoxan salts hydrates or polymorphs thereof issued 3 March 2008 assigned to Pierre Fabre Medicament 2 3 Dihydro 1 4 benzodioxin 2 carbimidic acid ethyl ester PubChem U S National Library of Medicine CID 10035919 nbsp This drug article relating to the nervous system is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Idazoxan amp oldid 1216939887, wikipedia, wiki, book, books, library,

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