Lack in effects of therapeutic concentrations of dexmedetomidine and clonidine on the neuromuscular blocking action of rocuronium in isolated rat diaphragms.

BACKGROUND We investigated the effects of the alpha-2 adrenoceptor agonists clonidine and dexmedetomidine on the neuromuscular blocking effect of rocuronium in vitro. METHODS Isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. RESULTS Clonidine and dexmedetomidine 50 microM (n = 6 each), but not 0.05 microM, shifted the rocuronium concentration-twitch tension curves to the left and decreased the rocuronium concentration for 50% twitch depression (IC50) compared with control (n = 9, P < 0.01). The leftward shift induced by clonidine 50 microM or dexmedetomidine 50 microM was not antagonized by yohimbine 50 microM, an alpha-2 adrenoceptor antagonist. Twitch tensions partially depressed by 7 microM rocuronium, to about 65% of the control, were further suppressed in a concentration-dependent manner by clonidine (n = 6) and dexmedetomidine (n = 9) at concentrations of 30 microM or more (P < 0.01). CONCLUSIONS These results indicate that very high, but not therapeutic, concentrations of clonidine and dexmedetomidine enhance the neuromuscular blocking action of rocuronium, but this is not mediated by an agonist action on alpha-2 adrenoceptors.