Atipamezole (MPV 1248)

Atipamezole is an antagonist of α_2A-adrenergic receptors (α_2A-ARs; K_i = 1.86 nM).^1,2 It is selective for α_2A-ARs over α_2B- and α₁-ARs (K_is = 1,949.83 and 13,300 nM, respectively), as well as over 40 receptors, ion channels, and transporters (IC₅₀s = 540->10,000 nM). Atipamezole (0.04, 0.08, and 1.2 mg/kg) reverses bradycardia and sedation induced by the α₂-AR agonist medetomidine in dogs.³ It also prevents hypoalgesia induced by the non-steroidal anti-inflammatory drug (NSAID) ketoprofen in sheep.⁴ Atipamezole (0.3 mg/kg) enhances contralateral circling behavior induced by apomorphine or L-DOPA and prolongs the duration of action of L-DOPA in a rat model of Parkinson’s disease.⁵ Formulations containing atipamezole have been used to reverse the sedative and analgesic effects of dexmedetomidine or medetomidine in dogs.

1.Vacher, B., Funes, P., Chopin, P., et al.Rigid analogues of the α2-adrenergic blocker atipamezole: Small changes, big consequencesJ. Med. Chem.53(19)6986-6995(2010) 2.Pertovaara, A., Haapalinna, A., Sirvi?, J., et al.Pharmacological properties, central nervous system effects, and potential therapeutic applications of atipamezole, a selective α2-adrenoceptor antagonistCNS Drug Rev.11(3)273-288(2005) 3.Vainio, O., and V?h?-Vahe, T.Reversal of medetomidine sedation by atipamezole in dogsJ. Vet. Pharmacol. Ther.13(1)15-22(1990) 4.Lizarraga, I., and Chambers, J.P.Involvement of opioidergic and α2-adrenergic mechanisms in the central analgesic effects of non-steroidal anti-inflammatory drugs in sheepRes. Vet. Sci.80(2)194-200(2006) 5.Haapalinna, A., Leino, T., and Heinonen, E.The α2-adrenoceptor antagonist atipamezole potentiates anti-Parkinsonian effects and can reduce the adverse cardiovascular effects of dopaminergic drugs in ratsNaunyn Schmiedebergs Arch. Pharmacol.368(5)342-351(2003)