Vatinoxan
Pharmaceutical compound
From Wikipedia, the free encyclopedia
Vatinoxan, originally known as MK-467, is an α2-adrenergic receptor antagonist used in veterinary medicine alongside α2-adrenergic receptor agonists to counteract vasoconstriction and hypertension while maintaining sedation.[1][2][3] Vatinoxan does not cross the blood–brain barrier giving it a unique pharmacological profile compared to the other α2-adrenergic receptor antagonists and distinct clinical application.[4]
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| Other names | MK 467; mk-467 free base; vatinoxanum |
| Drug class | Alpha blocker |
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| Formula | C20H26N4O4S |
| Molar mass | 418.51 g·mol−1 |
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Medical uses
Vatinoxan mitigates the cardiovascular depression caused by medetomidine and dexmedetomidine, although hypotension may still occur.[4][5][6][7][8][9] Administration of dobutamine, norepinephrine, or phenylephrine has been shown to restore normotension.[4][10][11]
Vatinoxan does not reduce central nervous system depression, as it is unable to cross the blood–brain barrier. However, it may influence the sedative effects of α2-adrenergic receptor agonists.[4]
Combination with medetomidine
A fixed-dose combination of medetomidine with vatinoxan (medetomidine/vatinoxan) is used to provide sedation whilst negating some of the negative cardiovascular effects of medetomidine.[4] This combination medication was approved in the US in 2022, and is sold under the brand name Zenalpha.[12]
Co-administration of vatinoxan and medetomidine improves recovery following atipamezole administration in sheep and dogs.[4][13][14]
Pharmacology
Vatinoxan binds to the α2-adrenergic receptor at a ratio of 105:1 over the α1-adrenergic receptor.[4] Vatinoxan appears to have no clinically relevant effect on the α1-adrenergic receptor based on a study in the horse and sheep.[15][4] Vatinoxan's low lipid solubility, molecular weight, ionisation, and protein binding cause it to poorly antagonise the α2-adrenergic receptors in the central nervous system whilst selectively antagonising peripheral and cardiovascular receptors. These properties make vatinoxan unique to the other α2-adrenergic receptor antagonists.[4]
Research
In a study on horses, vatinoxan administration was found to reduce medetomidine-induced sedation, which the authors hypothesised was due to altered clearance of medetomidine.[4][16] Conversely, a study in sheep reported that co-administration of vatinoxan and medetomidine enhanced sedation.[4][13]
Vatinoxan may also counteract the severe respiratory effects caused by α2-adrenergic receptor agonists in sheep.[4][17][18]
Additionally, vatinoxan has been shown to reduce the minimum alveolar concentration (MAC) of isoflurane and sevoflurane in two studies, although the underlying mechanism remains unclear and warrants further investigation.[4][19][20]
