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 treatment of depression. Baseline MHPG excretion (day 0) showed a significant 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 time interval. Twenty-four hours after the dose (dose was given at 0800 h), urinary MHPG levels returned to baseline, consistent with a reversible 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 Wiley-Liss, Inc.