Idazoxan

Research

Alzheimer’s disease

Mice treated with idazoxan, which blocks the α2A-adrenergic receptor, 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 disease pathology and symptoms in two mouse models, potentially offering an immediate treatment for this devastating disease.

Synthesis

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

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, (4). Treatment with ethylenediamine [107-15-3] (5) gives the imidazoline ring affording ** (6).

Veterinary use

Idazoxan has been used to reverse xylazine in cattle and sheep but it is rarely used in practice with other α2-adrenergic receptor antagonists such as yohimbine and atipamezole being used instead.

References

References

1. (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.
2. (2002). "RX 821002 as a tool for physiological investigation of alpha(2)-adrenoceptors". CNS Drug Reviews.
3. (1988). "Idazoxan and brain alpha2-adrenoceptor in the rabbit". Brain Research.
4. (1991). "Imidazole binding sites in rabbit kidney and forebrain membranes". J Auton Pharmacol.
5. (January 2020). "β-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3β/tau cascade". Science Translational Medicine.
6. (January 1981). "2-[2-(1, 4-benzodioxanyl)]-2-imidazoline hydrochloride.". Tetrahedron Letters.
7. (January 1984). "An investigation of some base induced transformations of the 1, 4-benzodioxan ring system.". Journal of Heterocyclic Chemistry.
8. (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.
9. "Certain 1, 4-benzodioxanyl imidazolines and corresponding pyrimidines and process".
10. "Pharmaceutical composition based on idazoxan, salts, hydrates or polymorphs thereof".
11. "2,3-Dihydro-1,4-benzodioxin-2-carbimidic acid ethyl ester". U.S. National Library of Medicine.
12. (11 September 2024). "Veterinary Anesthesia and Analgesia, The 6th Edition of Lumb and Jones". Wiley Blackwell.