体外研究
(In Vitro) | MAO-B-IN-6 (compound D5) (Sf9 cells) shows inhibitory activities towards monoamine oxidase (MAO) with theIC50s of 46.365 μM and 0.019 μM for MAO-A and MAO-B, respectively[1].
MAO-B-IN-6 shows no inhibition potential towards cytochrome P450 (IC50=>29 μM for 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5 enzymes)[1].
MAO-B-IN-6 (10 μM) shows high permeability through MDR1-MDCK II cell monolayers[1].
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体内研究
(In Vivo) | MAO-B-IN-6 (1 mg/kg, i.v.; 5 mg/kg, p.o.) shows oral bioavailability in rats (F=55.2%) and monkeys (F=107.1%)[1].
MAO-B-IN-6 (0.08, 0.4, 2 mg/kg; i.p.) diaplays stronger MAO-B inhibitory activity[1].
MAO-B-IN-6 (0.625, 1.25, 2.5 mg/kg; i.p.) increases the rearing activity in a dose-dependent manner[1].
MAO-B-IN-6 (0.625, 1.25, 2.5 mg/kg; i.p.) shows a potential efficacy for alleviating dopamine (DA) deficits in the MPTP-induced Parkinson's disease (PD) mouse model[1].
MAO-B-IN-6 (0.156, 0.312, 0.625, 1.25 mg/kg; i.p.) increases the effect of levodopa on dopamine concentration in the striatum[1].
MAO-B-IN-6 (0.156, 0.312, 0.625, 1.25 mg/kg; i.p.) shows a significant reduction in galantamine-induced tremulous jaw movements[1].
Pharmacokinetic Parameters of MAO-B-IN-6 in SD rats and cynomolgus monkeys[1].
| Compound | Route | Dose (mg/kg) | Cmax(ng/mL) | AUCt(ng·h/mL) | T1/2(h) | Vss (h) | Cl (mL/min/kg) | F (%) | | D5 (Rats) | iv | 1 | 690 | 505 | 0.67 | 1.37 | 32.9 | / | | D5 (Rats) | po | 5 | 1000 | 1400 | 0.57 | / | / | 55.2 | | D5 (Monkeys) | iv | 1 | 924 | 2120 | 1.77 | 1.06 | 7.54 | / | | D5 (Monkeys) | po | 5 | 2280 | 11,300 | 2.80 | / | / | 107.1 |
SD rats; 1 mg/kg, i.v.; 5 mg/kg, p.o.; Cynomolgus monkeys; 1 mg/kg, i.v.; 5 mg/kg, p.o. [1].
| Animal Model: | SD rats[1] | | Dosage: | 1, 5 mg/kg | | Administration: | 1 mg/kg, i.v.; 5 mg/kg, p.o. | | Result: | Showed oral bioavailability in rats (F=55.2%). |
| Animal Model: | cynomolgus monkeys[1] | | Dosage: | 1, 5 mg/kg | | Administration: | 1 mg/kg, i.v.; 5 mg/kg, p.o. | | Result: | Showed oral bioavailability in monkeys (F=107.1%). |
| Animal Model: | mice[1] | | Dosage: | 0.08, 0.4, 2 mg/kg | | Administration: | i.p. | | Result: | Displayed stronger MAO-B inhibitory activity. |
| Animal Model: | PD mouse mode[1] | | Dosage: | 0.625, 1.25, 2.5 mg/kg | | Administration: | i.p. | | Result: | Increased the rearing activity in a dose-dependent manner. |
| Animal Model: | C57BL/6 mice[1] | | Dosage: | 0.156, 0.312, 0.625, 1.25 mg/kg | | Administration: | i.p. | | Result: | Increased the effect of levodopa on dopamine concentration in the striatum. |
| Animal Model: | SD rats[1] | | Dosage: | 0.156, 0.312, 0.625, 1.25 (3.0 mg/kg galantamine, i.p.) | | Administration: | i.p. | | Result: | Showed a significant reduction in galantamine-induced tremulous jaw movements. |
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