The present study evaluated the relationship between the degree of
catechol-O-methyltransferase (COMT) inhibition in erythrocytes and liver by
BIA 3-202 (1-[3,4-dihydroxy-5-nitrophenyl]-2-phenyl-ethanone) and determined its effects upon the O-methylation of
L-DOPA in rats orally treated with
L-DOPA plus
benserazide. The soluble form of COMT (S-COMT) in erythrocytes was endowed with the same affinity as liver S-COMT for the substrate
adrenaline.
BIA 3-202 inhibited erythrocytes and liver S-COMT with ED50's of 1.9 (0.7, 3.1) and 1.9 (0.5, 3.2) (95% confidence limits) mg kg(-1), respectively.
BIA 3-202 reduced the
L-DOPA-induced rise of 3-O-methyl-L-DOPA in the peripheral circulation, striatal
dialysate levels and striatum, and increased
dopamine striatal levels. In BIA 3-202-treated rats the increase in
L-DOPA in peripheral blood and striatal
dialysates was significantly greater than in vehicle-treated rats. It is concluded that S-COMT activity in erythrocytes may provide important information on the pharmacodynamic profile of COMT inhibitors. The novel COMT inhibitor
BIA 3-202 is a potent COMT inhibitor that enhances the availability of
L-DOPA to the brain by reducing its O-methylation, which may prove beneficial in patients with
Parkinson's disease treated with
L-DOPA.