Mivazerol inhibits intrathecal release of glutamate evoked by halothane withdrawal in rats.
BACKGROUND
Mivazerol is a new and selective alpha 2-adrenergic receptor agonist devoid of hypotensive effects (1, 2). Previous studies have demonstrated that mivazerol prevents hemodynamic instability during emergence from halothane anesthesia in rats (3). The present study was to determine whether glutamate and aspartate are involved in this action of mivazerol, at the second to third thoracic segments (T2-T3) of the spinal cord.


METHODS
In vivo microdialysis in combination with high-performance liquid chromatography (HPLC) was employed in the study. Blood pressure (BP) and heart rate (HR) were recorded along with intrathecal (i.t.) microdialysis perfusion.


RESULTS
BP, HR and i.t. release of glutamate (GLU, pmol/microliter) were stable in the rats under 1.1% halothane anesthesia. However, halothane withdrawal immediately increased BP, HR, and i.t. release of GLU, and remained elevated for at least 2 h after withdrawal of halothane. Thirty minutes prior to halothane withdrawal, intravenous (i.v.) infusion of mivazerol (15 micrograms.kg-1.h-1) almost completely prevented the increases in HR (delta 18 +/- 7 vs delta 79 +/- 7 beats/min), and in the i.t. release of GLU (delta 10.3 +/- 3.7 vs delta 30.6 +/- 5.9; 112% vs 167%). Local i.t. microinjection of mivazerol (2.5 micrograms/kg) 2 min prior to withdrawal of halothane also blocked the HR responses, as well as on the i.t. release of GLU following halothane withdrawal.


CONCLUSIONS
The present study demonstrates that emergence from halothane anesthesia increases i.t. release of GLU, and that mivazerol has an inhibitory effect on the above, through its direct action on the spinal cord.
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
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Zhang
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Kindel
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Wülfert
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Hanin
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006221:Halothane / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D018685:Anesthetics, Inhalation; D007093:Imidazoles; D001224:Aspartic Acid; D018698:Glutamic Acid; D006221:Halothane; C087969:mivazerol