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.

CONCLUSION

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.