Abstract
Amiflamine, a reversible and selective monoamine oxidase-A (MAO-A) inhibitor, was examined with respect to its metabolism and MAO inhibitory effects in the rat. The rats were divided into three groups, 1) control (amiflamine 5 mg/kg p.o.), 2) phenobarbital pretreated and 3) SKF 525-A pretreated. Concentrations of amiflamine and its main metabolite, FLA 788 and the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain were measured using HPLC. Thein vitroMAO-A inhibitory effect of FLA 788 was about 10 times more potent than that of amiflamine. Peak concentration (Cmax) and the area under the curve (AUC) of amiflamine in brain were decreased in the phenobarbital pretreated group and increased in the SKF 525-A pretreated group, whereas those of FLA 788 were decreased in both groups. The increase in brain 5-HT content was potentiated in the SKF 525-A pretreated group and suppressed in the phenobarbital pretreated group. Therefore, the relative increase in 5-HT content in the SKF 525-A pretreated group was probably due to the increased AUC for amiflamine in the brain. These results suggest that contrary to the resultsin vitro, amiflamine is possibly more potent than FLA 788in vivoin the rat brain.
