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  • Title: Rapid reversal of alpha 2-adrenoceptor agonist effects by atipamezole in human volunteers.
    Author: Karhuvaara S, Kallio A, Salonen M, Tuominen J, Scheinin M.
    Journal: Br J Clin Pharmacol; 1991 Feb; 31(2):160-5. PubMed ID: 1675577.
    Abstract:
    1. The ability of atipamezole, a specific and selective alpha 2-adrenoceptor antagonist, to reverse the pharmacological effects induced by the alpha 2-adrenoceptor agonist dexmedetomidine was studied in six healthy male volunteers. Each volunteer received in four sessions in a randomized and single-blind manner three different doses (6.7 micrograms kg-1, 27 micrograms kg-1 and 67 micrograms kg-1) of atipamezole or saline placebo as 5 min i.v. infusions preceded by a fixed i.v. dose of dexmedetomidine (0.67 micrograms kg-1). 2. Dexmedetomidine caused profound sedation, with the subjects actually falling asleep. This was effectively reversed by the two highest doses of antipamezole. 3. Dexmedetomidine reduced salivary flow on average by 70%. A rapid and full reversal of this effect was seen after the highest dose of antipamezole. 4. Hypotension induced by dexmedetomidine was also effectively antagonized by atipamezole. Bradycardia was very modest after dexmedetomidine in this study, and thus no reversal of alpha 2-adrenoceptor agonist-induced bradycardia could be demonstrated. 5. Plasma noradrenaline concentrations were reduced by 80% by dexmedetomidine. This was effectively antagonized by atipamezole, and the highest dose caused a 50% overshoot in plasma noradrenaline concentrations over the basal levels. 6. It is concluded that the effects of dexmedetomidine are effectively reversible by atipamezole. A dose ratio of 10:1 for atipamezole:dexmedetomidine was clearly insufficient for this purpose, but ratios in the range of 40:1 to 100:1 were found to be effective in the current experimental situation.
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