Bernserazide (D,
L-serine 2-[2,3,4-trihydroxybenzyl]-
hydrazide) as been shown to inhibit the
clorgyline-resistant amine oxidase (CRAO) activities which metabolize
benzylamine in homogenates of rat aorta, heart and brown adipose tissue. In vitro studies showed a concentration- and time-dependent inhibition of CRAO in heart and aorta which was reversed by dialysis for 18hr. At high concentrations (10(-4)-10(-3)M)
benserazide appeared to increase
enzyme activity towards and occasionally above control value. These increases became more prominent after long periods of preincubation (especially in the presence of saturating
benzylamine concentrations) and remained after dialysis of those homogenates preincubated with
benserazide. The administration of
benserazide for one or seven days in daily doses of 5-150 mg/kg also inhibited CRAO activity in vivo in a dose-dependent manner, with greater inhibition after seven days treatment. Reversal of inhibition, by dialysis of tissue homogenates from
benserazide-treated rats, was much slower than was found with homogenates incubated in vitro with the
drug. After
benserazide administration to rats,
MAO-A activity towards
5-hydroxytryptamine was generally not inhibited, and in fact was significantly increased in some cases. The administration of
L-DOPA (250 mg/kg) together with
benserazide (40 mg/kg) resulted in a similar degree of CRAO inhibition in aorta and heart to that seen after
benserazide alone. These findings are discussed with regard to the use of these drugs in the
therapy of
Parkinson's Disease, although the paucity of information about the physiological function of CRAO makes the significance of its inhibition by
benserazide unclear.