Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat.
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)
Weinger
M B
MB
Department of Anesthesiology, Veterans Administration Medical Center, San Diego, California 92161.
Segal
I S
IS
Maze
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M
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D015760:Alfentanil; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020926:Medetomidine; D009127:Muscle Rigidity / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D004146:Dioxanes; D007093:Imidazoles; D015760:Alfentanil; C032368:midaglizole; D020926:Medetomidine; D005283:Fentanyl; D019329:Idazoxan