PF 9601N
目录号 : GC49201
An inhibitor of MAO-B
Cas No.:133845-63-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
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- Datasheet
PF 9601N is an inhibitor of monoamine oxidase B (MAO-B).1 It selectively inhibits MAO-B in mouse brain homogenates ex vivo (ID50 = 381 nmol/kg) and prevents MPTP-induced reductions in dopamine levels in the striatum of 8- to 9-week-old mice when administered at doses ranging from 29.5 to 8.47 µmol/kg. PF 9601N (0.027 µmol/kg) prevents MPTP-induced lesions in 9- to 10-month-old mice. It also increases the duration of contralateral rotational behavior induced by L-DOPA in a rat model of Parkinson’s disease induced by 6-OHDA when administered at doses of 40 and 60 mg/kg.2
1.Perez, V., and Unzeta, M.PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], a new MAO-B inhibitor, attenuates MPTP-induced depletion of striatal dopamine levels in C57/BL6 miceNeurochem. Int.42(3)221-229(2003) 2.Prat, G., PÉrez, V., Rubi, A., et al.The novel type B MAO inhibitor PF9601N enhances the duration of L-DOPA-induced contralateral turning in 6-hydroxydopamine lesioned ratsJ. Neural Transm. (Vienna)107(4)409-417(2000)
| Cas No. | 133845-63-3 | SDF | |
| Canonical SMILES | C#CCNCC1=CC2=C(N1)C=CC(OCC3=CC=CC=C3)=C2 | ||
| 分子式 | C19H18N2O | 分子量 | 290.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:3): 0.25 mg/ml,Ethanol: 20 mg/ml | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4435 mL | 17.2176 mL | 34.4353 mL |
| 5 mM | 0.6887 mL | 3.4435 mL | 6.8871 mL |
| 10 mM | 0.3444 mL | 1.7218 mL | 3.4435 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], a new MAO-B inhibitor, attenuates MPTP-induced depletion of striatal dopamine levels in C57/BL6 mice
Neurochem Int 2003 Feb;42(3):221-9.PMID:12427476DOI:10.1016/s0197-0186(02)00091-8.
Monoamine oxidase isoform B (MAO-B) is involved in Parkinson's disease (PD) induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxin (MPTP) in human and non-human-primate. MAO-B inhibitors, such as L-deprenyl have shown to prevent against MPTP-toxicity in different species, and it has been used in Parkinson therapy, however, the fact that it is metabolized to (-)-methamphetamine and (-)-amphetamine highlights the need to find out new MAO-B inhibitors without a structural amphetaminic moiety. In this context we herein report, for the first time, anywhere a novel non-amphetamine-like MAO-B inhibitor, PF 9601N, N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine. This attenuates the MPTP-induced striatal dopamine depletion in young-adult and adult-old C57/BL mice, using different schedules of administration, and which behave "ex vivo" as a slightly more potent and selective MAO-B inhibitor than L-deprenyl, assayed for comparative purposes in the same experimental conditions. The MAO-B ID(50) values were calculated from the total MAO-B activity measured against [14C] phenylethylamine (22 microM) as substrate, at each inhibitor concentration. The MAO-B ID(50) values resulted to be 381 and 577 nmol/kg for PF 9601N and L-deprenyl, respectively. The intraperitoneally (i.p.) co-administration to young-adult C57/BL6 mice of MPTP (30 mg/kg), with different concentrations of PF 9601N or L-deprenyl (29.5-0.357 micromol/kg) showed a dose-dependent protective effect against striatal dopamine depletion, measuring the dopamine contents and its metabolites by HPLC. The ED(50) value proved to be 3.07 micromol/kg without any significant differences between either MAO-B inhibitor. Nevertheless, lower doses of PF 9601N (1.5 micromol/kg) were necessary to get almost total protection, without any change in the DOPAC and HVA content, when administered 2 h before MPTP (30 mg/kg), whereas partial protection (45%) against dopamine depletion was observed in the case of L-deprenyl. In both cases, MAO-B inhibition was a necessary condition in order to observe the protective effect. When adult-old (8-10 months) C57/BL6 mice were used, MPTP (25 mg/kg) administration induced 25 days later, an irreversible dopamine depletion. In these conditions, chronic administration with 0.15 micromol/kg of PF 9601N, before the toxin, every 24 h for 10 days, rendered almost total protection of dopamine depletion, whereas L-deprenyl yielded only 50% protection of the dopamine content, assayed in the same conditions. It is worth remarking, that in both cases MAO-B was not affected. From these results, it can be concluded that PF 9601N attenuates MPTP neurotoxicity "in vivo" better than L-deprenyl through different mechanisms, with special relevance to the protective effect, independent of MAO-B inhibition, observed in the irreversibly MPTP-lesioned adult-old mice. Therefore, this novel non-amphetamine MAO-B inhibitor could be potentially effective in PD therapy.
Multi-Target Directed Donepezil-Like Ligands for Alzheimer's Disease
Front Neurosci 2016 May 25;10:205.PMID:27252617DOI:10.3389/fnins.2016.00205.
HIGHLIGHTS ASS234 is a MTDL compound containing a moiety from Donepezil and the propargyl group from the PF 9601N, a potent and selective MAO B inhibitor. This compound is the most advanced anti-Alzheimer agent for preclinical studies identified in our laboratory.Derived from ASS234 both multipotent donepezil-indolyl (MTDL-1) and donepezil-pyridyl hybrids (MTDL-2) were designed and evaluated as inhibitors of AChE/BuChE and both MAO isoforms. MTDL-2 showed more high affinity toward the four enzymes than MTDL-1.MTDL-3 and MTDL-4, were designed containing the N-benzylpiperidinium moiety from Donepezil, a metal- chelating 8-hydroxyquinoline group and linked to a N-propargyl core and they were pharmacologically evaluated.The presence of the cyano group in MTDL-3, enhanced binding to AChE, BuChE and MAO A. It showed antioxidant behavior and it was able to strongly complex Cu(II), Zn(II) and Fe(III).MTDL-4 showed higher affinity toward AChE, BuChE.MTDL-3 exhibited good brain penetration capacity (ADMET) and less toxicity than Donepezil. Memory deficits in scopolamine-lesioned animals were restored by MTDL-3.MTDL-3 particularly emerged as a ligand showing remarkable potential benefits for its use in AD therapy. Alzheimer's disease (AD), the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills, and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, β-amyloid deposits, τ-protein phosphorylation, oxidative stress, and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept®) but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands (MTDL) based on the "one molecule, multiple targets" paradigm. Thus, in this context, different series of novel multifunctional molecules with antioxidant, anti-amyloid, anti-inflammatory, and metal-chelating properties able to interact with multiple enzymes of therapeutic interest in AD pathology including acetylcholinesterase, butyrylcholinesterase, and monoamine oxidases A and B have been designed and assessed biologically. This review describes the multiple targets, the design rationale and an in-house MTDL library, bearing the N-benzylpiperidine motif present in donepezil, linked to different heterocyclic ring systems (indole, pyridine, or 8-hydroxyquinoline) with special emphasis on compound ASS234, an N-propargylindole derivative. The description of the in vitro biological properties of the compounds and discussion of the corresponding structure-activity-relationships allows us to highlight new issues for the identification of more efficient MTDL for use in AD therapy.
Neuroprotective effect of the monoamine oxidase inhibitor PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine] on rat nigral neurons after 6-hydroxydopamine-striatal lesion
Neurosci Lett 2002 Aug 30;329(2):165-8.PMID:12165403DOI:10.1016/s0304-3940(02)00614-6.
Monoamine oxidase B (MAO-B) inhibitors are potentially useful in the therapeutic treatment of Parkinson's disease. L-Deprenyl has been shown to slow nigrostriatal tract degeneration in human idiopathic Parkinsonism and to be an effective neuroprotector in experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity models. However, L-amphetamine and (-)methamphetamine, the metabolites generated by L-deprenyl, can have adverse and severe side-effects. Therefore, the search for new MAO-B inhibitors without potential amphetamine-like properties is a matter of great therapeutic interest. The present report is the first to describe the neuroprotective effect--following chronic intraperitoneal (i.p.) treatment--of a novel and non-amphetaminic MAO-B inhibitor, [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine] (PF 9601N), on the neurodegeneration of nigral dopaminergic neurons caused by administration of intrastriatal 6-hydroxydopamine (6-OHDA). Two groups of six animals were unilaterally injected with 6-OHDA in the right striatum. One group was treated daily with 60 mg/kg PF 9601N i.p., starting before stereotaxic lesion and continuing for 18 days thereafter. The other group was treated with vehicle solution. Coronal slabs including the substantia nigra pars compacta (SNpc) were processed for tyrosine hydroxylase immunohistochemistry (TH). The number of TH positive (TH+) neurons in the SNpc was 60% lower in 6-OHDA lesioned rats. However, the loss of TH+ neurons in the SNpc was only 30% in PF 9601N i.p.-treated animals. Therefore, treatment with the specific MAO-B inhibitor significantly reduced the 6-OHDA-induced degeneration to about 50%.
Protective effect of N-(2-propynyl)-2-(5-benzyloxyindolyl) methylamine (PF 9601N), a novel MAO-B inhibitor, on dopamine-lesioned PC12 cultured cells
J Pharm Pharmacol 2003 May;55(5):713-6.PMID:12831516DOI:10.1211/002235703765344649.
Oxidative stress may play a role in the pathogenesis of Parkinson's disease. We have standardised a new model of dopaminergic-cell toxicity that uses dopamine, which is able to generate free radicals, as a toxin. The effect of this catecholamine on cell viability (MTT staining) was dose-dependent, reaching 65% of cell loss at a dopamine concentration of 300 microM. In this model, the protective effect of a novel MAO-B inhibitor, N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine (PF 9601N), was studied and compared with the effect of L-deprenyl assayed under the same experimental conditions. Whereas PF 9601N (50 microM and 100 microM) showed a significant protective effect, this was not the case with L-deprenyl. This different behaviour could be explained in terms of difference in antioxidant capacity. The toxicity induced in PC12 cells by 300 microM dopamine was partially reversed by incubating it in the presence of GBR-12909, a dopamine-transporter blocker. The results indicated that, besides the intracellular toxicity effect of dopamine, another non-specific extracellular mechanism could be involved.
Indolalkylamines derivatives as antioxidant and neuroprotective agents in an experimental model of Parkinson's disease
Med Sci Monit 2004 Dec;10(12):BR477-84.PMID:15567979doi
Background: The neuroprotective effect of N-(2-propynyl)2-(5-benzyloxy-indol)methylamine (PF 9601N), a novel MAO B inhibitor, and its metabolite FA 72 on the human neuroblastoma SHSY5Y cell line lesioned with (300 microM) dopamine was assessed and compared with that of 1-deprenyl assayed at identical experimental conditions. Material/methods: Using this experimental model, PF 961N showed a neuroprotective effect in a dose-dependent manner, and at a concentration of 10 pM a 20% recovery of cell viability was observed. However, the metabolite FA72 assayed under the same experimental conditions showed an increase in cell viability of nearly 50%. In the case of l-deprenyl, a concentration of 100 microM was necessary to recover only 10% of cell viability. Results: This neuroprotective effect could be explained in terms of the antioxidant capacity of PF 9601N. In this context, the antioxidant capacities of the novel series of MAO inhibitors, PF 9601N and its analogues, were evaluated by their inhibition of the auto-oxidation of dopamine to melanin and by the dichlorofluorescein and 2-deoxyribose methods. Conclusions: All of these compounds have the basic structure of an indole ring in common, but show different substituents at different positions in it. The corresponding structure-activity relationship studies allowed us to conclude that the presence of a benzyloxy group, or a hydroxy or methoxy group, at position 5 of the indol ring enhanced these antioxidant characteristics, presenting a decreasing order of antioxidant activity of the primary > secondary > tertiary amines. The antioxidant properties of PF 9601 N would explain its neuroprotective effect observed in SHSY5Y cells lesioned with dopamine.