Abstract
The effects of various local anesthetics on rat brain and liver monoamine oxidase (MAO) and their antihemolytic and local anesthetic effects were studied. All local anesthetics tested at 1×10-7 M to 1×10-3 M inhibited MAO activity in rat liver mitochondria with 5-hydroxytryptamine (5-HT) as substrate. The order of potency was tetracaine>procaine> dibucaine>lidocaine>prilocaine. Tetracaine and procaine inhibited 5-HT oxidation much more than β-phenylethylamine (PEA) oxidation. Dibucaine inhibited PEA oxidation as much as 5-HT oxidation. Inhibition of MAO by local anesthetics other than dibucaine was reversible. Tetracaine and procaine inhibited 5-HT oxidation competitively, whereas dibucaine inhibited it non-competitively. Antihemolytic effects were observed with dibucaine and tetracaine at concentrations of 6 × 10-5 M and 1×10-4 M, respectively. The order of surface anesthetic potencies was dibucaine>tetracaine> prilocaine>lidocaine>procaine. These results suggest that the inhibition of MAO activities by local anesthetics depends on both electrostatic and hydrophobic interactions between these drugs and enzyme-associated phospholipids or the hydrophobic regions of proteins.
