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ANESTHETIC PHARMACOLOGY

Lack in Effects of Therapeutic Concentrations of Dexmedetomidine and Clonidine on the Neuromuscular Blocking Action of Rocuronium in Isolated Rat Diaphragms

Eichi Narimatsu, MD, PhD^*, Tomohisa Niiya, MD, PhD^*, Mikito Kawamata, MD, PhD^*, and Akiyoshi Namiki, MD, PhD^*

From the Departments of *Anesthesiology and Traumatology and Critical Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

Address correspondence and reprint requests to Dr. Eichi Narimatsu, MD, PhD, Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. Address e-mail to enarimat{at}sapmed.ac.jp.

BACKGROUND: We investigated the effects of the -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 µM (n = 6 each), but not 0.05 µM, 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 µM or dexmedetomidine 50 µM was not antagonized by yohimbine 50 µM, an -2 adrenoceptor antagonist. Twitch tensions partially depressed by 7 µM 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 µM 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 -2 adrenoceptors.