Atipamezole

Atipamezole (brand name Antisedan) is a synthetic α2 adrenergic receptor antagonist indicated for the reversal of the sedative and analgesic effects of dexmedetomidine and medetomidine in dogs. Its reversal effect works by competing with the sedative for α2-adrenergic receptors and displacing them. It is mainly used in veterinary medicine, and while it is only licensed for dogs and for intramuscular use, it has been used intravenously, as well as in cats and other animals. There is a low rate of side effects, largely due to atipamezole's high specificity for the α2-adrenergic receptor. Atipamezole has a very quick onset, usually waking an animal up within 5 to 10 minutes. Atipamezole (brand name Antisedan) is a synthetic α2 adrenergic receptor antagonist indicated for the reversal of the sedative and analgesic effects of dexmedetomidine and medetomidine in dogs. Its reversal effect works by competing with the sedative for α2-adrenergic receptors and displacing them. It is mainly used in veterinary medicine, and while it is only licensed for dogs and for intramuscular use, it has been used intravenously, as well as in cats and other animals. There is a low rate of side effects, largely due to atipamezole's high specificity for the α2-adrenergic receptor. Atipamezole has a very quick onset, usually waking an animal up within 5 to 10 minutes. It was originally released in 1996 and is sold in the U.S. by Zoetis. Atipamezole is a veterinary drug whose prime purpose is to reverse the effects of the sedative dexmedetomidine (as well as its racemic mixture, medetomidine). It can also be used to reverse the related sedative xylazine. While it reverses both the sedative and analgesic (pain-relieving) effects of dexmedetomidine, atipamezole may not entirely reverse the cardiovascular depression that dexmedetomidine causes. Atipamezole is licensed in the United States for intramuscular injection (IM) in dogs; it is, however, used off-label in cats, rabbits, and farm animals such as horses and cows, as well as in zoo medicine for reptiles (including tortoises, turtles, and alligators), armadillos, hippopotamuses, giraffes, okapi, and others. It has been given intravenously (IV), subcutaneously, intraperitonealy and, in red-eared sliders, intranasally. IV administration is recommended in emergencies. Atipamezole has also been used as an antidote for various toxicities in dogs. For example, the anti-tick medication amitraz is commonly ingested by dogs who eat their anti-tick collars. Amitraz works by the same mechanism as dexmedetomidine and is thus easily reversed by atipamezole. Atipamezole also reverses the hypotension caused by tizanidine (a muscle relaxant) toxicity, and relieves toxicity from decongestants such as ephedrine and pseudoephedrine. Atipamezole is sold at 5 mg/mL for ease of use: 5 times as much atipamezole as medetomidine is needed for full reversal, and because medetomidine is sold as 1 mg/mL, 1 mL of atipamezole reverses 1 mL of medetomidine. When the enantiomerically pure version of medetomidine (dexmedetomidine) was released, it was sold at 0.5 mg/mL, because it was twice as strong as medetomidine. As such, 1 mL of atipamezole also reverses 1 mL of dexmedetomidine. Atipamezole is not recommended for animals that are pregnant, lactating, or slated for breeding. While there are no absolute contraindications to atipamezole, it is recommended against being given with anticholinergics, as both can cause dramatic increases in heart rate. Atipamezole should also not be given too soon after an animal has been given dexmedetomidine mixed with ketamine or telazol(tiletamine); because it reverses only the dexmedetomidine, the ketamine or telazol will still be active, and the animal can wake up excited, delirious, and with muscle contractions. Some recommend not using it in dogs sedated with ketamine at all, since they can convulse due to the excitement effect. Atipamezole's low rate of side effects is due to its high specificity for ɑ2-adrenergic receptors; it has very little affinity for ɑ1-adrenergic receptors and no affinity for most serotonin, muscarinic, and dopamine receptors. There is occasional vomiting, hypersalivation, and diarrhea. It can potentially cause CNS excitement, which can lead to tremors, tachycardia (increased heart rate), and vasodilation. The vasodilation leads to a transient decrease in blood pressure, which (in dogs) increases to normal within 10 minutes. There have been reports of transient hypoxemia. The chance of side effect can be minimized by administering atipamezole slowly.