Effects of intrathecally administered dexmedetomidine, MPV-2426 and tizanidine on EMG in rats.
BACKGROUND
When administered intrathecally, alpha-2 adrenergic agonists produce spinally mediated antinociception, but also rapidly redistribute to supraspinal sites. This investigation the compared EMG effects of intrathecally administered dexmedetomidine, MPV-2426 (fadolmidine), and tizanidine in Sprague-Dawley rats, which has not been previously described.


METHODS
We studied electromyographic (EMG) responses of the head and gastrocnemius muscles, antinociception using the tail-flick test, and sedation by using observer assessment. Saline, dexmedetomidine (0.5 microg, 2.5 microg and 12.5 microg), MPV-2426 (2 microg, 10 microg and 50 microg) and tizanidine (2 microg, 10 microg and 50 microg) were administered intrathecally.


RESULTS
Tizanidine 50 microg, MPV-2426 10 microg and 50 microg, and dexmedetomidine 2.5 microg and 12.5 microg, decreased EMG activity (P < 0.005). Dexmedetomidine 12.5 microg, MPV-2426 50 microg, and tizanidine 10 microg and 50 microg increased tail-flick latencies (P < 0.01). Dexmedetomidine alone significantly increased the magnitude of observer-assessed sedation (P < 0.0001).


CONCLUSIONS
We conclude that in rats, intrathecally administered dexmedetomidine, MPV-2426 and tizanidine have dose-dependent effects on EMG. At antinociceptive doses, the EMG effects of these three alpha-2 adrenergic agonists differ (dexmedetomidine > MPV-2426 > tizanidine).
Talke
P
P
Departments of Anesthesia and Perioperative Medicine, University of California, San Francisco, CA 94143-0648, USA. talkep@anesthesia.ucsf.edu
Xu
M
M
Paloheimo
M
M
Kalso
E
E
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000187:drug effects; D006993:Hypnotics and Sedatives; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D007189:Indans; D020927:Dexmedetomidine; C023754:tizanidine; D003000:Clonidine; C400294:radolmidine