Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat

Anesthesiology. 1989 Aug;71(2):242-9. doi: 10.1097/00000542-198908000-00013.

Abstract

The highly-selective alpha-2 adrenergic agonist dexmedetomidine (D-MED) is capable of inducing muscle flaccidity and anesthesia in rats and dogs. Intense generalized muscle rigidity is an undesirable side effect of potent opiate agonists. Although the neurochemistry of opiate-induced rigidity has yet to be fully elucidated, recent work suggests a role for a central adrenergic mechanism. In the present study, the authors determined if treatment with D-MED prevents the muscle rigidity caused by high-dose alfentanil anesthesia in the rat. Animals (n = 42) were treated intraperitoneally with one of the following six regimens: 1) L-MED (the inactive L-isomer of medetomidine), 30 micrograms/kg; 2) D-MED, 10 micrograms/kg; 3) D-MED, 30 micrograms/kg; 4) D-MED [30 micrograms/kg] and the central-acting alpha-2 antagonist, idazoxan [10 mg/kg]; 5) D-MED [30 micrograms/kg] and the peripheral-acting alpha-2 antagonist DG-5128 [10 mg/kg], or; 6) saline. Baseline electromyographic activity was recorded from the gastrocnemius muscle before and after drug treatment. Each rat was then injected with alfentanil (ALF, 0.5 mg/kg sc). ALF injection resulted in a marked increase in hindlimb EMG activity in the L-MED treatment group which was indistinguishable from that seen in animals treated with saline. In contrast, D-MED prevented alfentanil-induced muscle rigidity in a dose-dependent fashion. The small EMG values obtained in the high-dose D-MED group were comparable with those recorded in earlier studies from control animals not given any opiate. The high-dose D-MED animals were flaccid, akinetic, and lacked a startle response during the entire experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / therapeutic use*
  • Adrenergic alpha-Antagonists / pharmacology
  • Alfentanil
  • Analgesics, Opioid / antagonists & inhibitors*
  • Animals
  • Dioxanes / pharmacology
  • Fentanyl / analogs & derivatives*
  • Fentanyl / antagonists & inhibitors
  • Idazoxan
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Male
  • Medetomidine
  • Muscle Rigidity / prevention & control*
  • Rats
  • Rats, Inbred Strains

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Analgesics, Opioid
  • Dioxanes
  • Imidazoles
  • Alfentanil
  • midaglizole
  • Medetomidine
  • Fentanyl
  • Idazoxan