MDL 72394

MDL 72394 (FMMT) (0.1-1 mg/kg; subcutaneous injection; single injection) showed a slight preference for MAO inhibition within noradrenergic and dopaminergic neurons, with ED₅₀ values of 0.24 and 0.20 mg/kg subcutaneously, respectively, but no such preference for serotonergic neurons^[1].
MDL 72394 (0.003-0.1 mg/kg; oral; once daily; 7 days) in combination with Carbidopa (HY-B0311) enhances the preference for MAO inhibition within noradrenergic and dopaminergic neurons, with ED₅₀ values of 0.016 and 0.010 mg/kg, respectively^[1].
MDL 72394 (0.05-0.1 mg/kg; oral; 24 h) in combination with the selective NA uptake inhibitor CPP 199 antagonizes the preferential inhibition of MAO within noradrenergic neurons by FMMT, indicating that this preference is due to the accumulation of the active metabolite by the NA transporter^[1].
MDL 72394 (0.5-2 mg/kg; intraperitoneal injection; single administration) produced the greatest increase in hypothalamic extracellular 5-HT, but even after L-tryptophan it failed to induce 5-HT behavioral syndrome, whereas MAO-A inhibition alone at 0.5 mg/kg was insufficient to elevate extracellular 5-HT or behavior^[2].
MDL 72394 (FMMT) (0.5 mg/kg; intraperitoneal injection) inhibits MAO in vivo, but this effect is abolished by pretreatment with MFMD to inhibit AADC, confirming that FMMT requires decarboxylation by AADC to inhibit MAO^[3].
MDL 72394 (0.1-0.5 mg/kg; intraperitoneal injection) is actively transported into the brain in vivo, as high-dose leucine attenuates its MAO inhibitory effect in the brain, but not in peripheral tissues^[3].
MDL 72394 (0.1 mg/kg; oral) in combination with carbidopa produced significantly less MAO inhibition in the 6-OHDA-lesioned striatum than in the intact striatum, indicating that FMMT is decarboxylated within dopamine-containing neurons of the nigrostriatal bundle; moreover, the MAO A inhibitory effect on the MFMD-infused side of the striatum was significantly reduced, confirming that neuronal AADC is essential for FMMT activation and neuronal selectivity^[3].
MDL 72394 (0.015-1 mg/kg; oral; daily; 5 days) in combination with Carbidopa produced brain MAO inhibition (-76%) and monoamine elevation comparable to higher doses of FMMT alone, but with significantly reduced tyramine potentiation, indicating that combination with a peripheral AADC inhibitor can reduce adverse tyramine interactions^[3].
MDL 72394 (MDL) (0.5 mg/kg; intraperitoneal injection; single administration) administered systemically stimulated melatonin biosynthesis in the rat pineal gland, increasing melatonin to 1.49 ng/pineal gland, most likely due to selective MAO-A inhibition caused by the decarboxylation product of MDL 72394, MDL 72392^[4].