EFFECT OF A NOVEL MONOAMINE OXIDASE-A INHIBITOR, BW 1370U87, ON URINARY 3-METHOXY-4-HYDROXYPHENYLGLYCOL IN NORMAL VOLUNTEERS

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were measured in 14 normal volunteers during a Phase I study of the novel, reversible monoamine oxidase-A (MAO-A) inhibitor BW 1370U87 targeted for the trea tment of depression. Baseline MHPG excretion (day 0) showed a signific ant diurnal increase (n = 14, P < 0.05) between 1200 and 2000 h. Oral administration of BW 1370U87 produced significant (35-45% maximal, P < 0.05) decreases from these basal levels during the same 1200-2000 h t ime interval. Twenty-four hours after the dose (dose was given at 0800 h), urinary MHPG levels returned to baseline, consistent with a rever sible mechanism of inhibition by BW 1370U87. Decreases in urinary MHPG did not appear to be dose-dependent between 200-800 mg BW 1370U87 per day, suggesting that maximal MAO-A inhibition was achieved at the 200 mg dose. These effects on MHPG excretion may be helpful in predicting the efficacy of BW 1370U87 in the treatment of depression. (C) 1993 W iley-Liss, Inc.