Plasma protein binding of the reversible type a MAO inhibitor cimoxatone (MD 780515)

Binding of a new selective reversible type A MAO inhibitor cimoxatone (MD 780515) to plasma proteins was studied in vitro by equilibrium dialysis. Binding to 580 μM human serum albumin (HSA) and to total plasma proteins was 93–96% and independent of cimoxatone concentration (0.15–207 μM). The drug was mainly bound to HSA with two binding sites and a moderate association constant ( K = 2.9 × 10 4 M −1). Free fatty acids did not modify cimoxatone binding to HSA. Cimoxatone was also moderately bound to isolated lipoprotein fractions; α 1-acid glycoprotein and γ-globulins did not play an important role in the binding of cimoxatone. MD 770222, the O-demethyl metabolite, appeared to be bound to HSA at the same binding sites as cimoxatone. However, no interaction occurred between the two compounds for 580 μM HSA. L-Tryptophan, bilirubin, the benzodiazepines flunitrazepam and oxazepam, imipramine and aspirin, did not displace cimoxatone from its binding sites. On the other hand, warfarin and phenylbutazone decreased cimoxatone binding to 29 μM HSA but no interaction occurred with 580 μM HSA.