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.