Ascorbic acid inhibits spinal meningeal catechol-o-methyl transferase in vitro, markedly increasing epinephrine bioavailability.
BACKGROUND
The spinal menings have previously been shown to contain catechol-o-methyl transferase (COMT), the enzyme that metabolizes epinephrine to the inactive metabolite metanephrine. The authors of this study aimed to quantitate the metabolism of epinephrine traversing the spinal meninges and to determine if that metabolism could be inhibited. In addition, they tried to determine the meningeal permeability of epinephrine.


METHODS
Macca nemestrina spinal meninges were mounted in a diffusion cell and epinephrine was added to the donor reservoir at time 0. Three hundred minutes later, all buffer in the recipient reservoir was collected and analyzed for epinephrine metabolites. The experiments were conducted with either ascorbic acid (1 mM) or sodium metabisulfite (5.3 mM) added as antioxidants.


RESULTS
In the presence of sodium metabisulfite, 60 +/- 6% of the epinephrine traversing the meningeal specimens was metabolized by COMT. In contrast, in the presence of ascorbic acid, less than 3% of the epinephrine traversing the spinal meninges was metabolized by COMT (P = 0.0001). The meningeal permeability coefficient for epinephrine was 0.38 +/- 0.08 cm/min x 10(-3).


CONCLUSIONS
Epinephrine permeability through the spinal meninges is low, and meningeal COMT markedly reduces the bioavailability of what little epinephrine can traverse the meninges. However, a clinically relevant concentration of ascorbic acid, a competitive inhibitor of COMT, almost completely blocks epinephrine metabolism and increases the bioavailability of epinephrine.
Kern
C
C
Department of Anesthesiology, University of Washington, Seattle 98195, USA.
Bernards
C M
CM
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001682:Biological Availability; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008254:Macaca nemestrina; D008297:Male; D008578:Meninges / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010539:Permeability; D013116:Spinal Cord / Q000378:metabolism*; D013447:Sulfites / Q000494:pharmacology
D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D013447:Sulfites; C030981:metabisulfite; D001205:Ascorbic Acid; D009638:Norepinephrine