Pargyline
(Synonyms: 优降宁) 目录号 : GC36853
An irreversible MAO inhibitor
Cas No.:555-57-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pargyline is an irreversible inhibitor of monoamine oxidase (MAO; Kis = 15 and 1.8 μM for MAO-A and MAO-B, respectively).1 At 10 mg/kg i.v., pargyline induces a moderate decrease of systolic blood pressure in unanaesthetized hypertensive rats but not normotensive WKR or Sprague-Dawley rats.2 The correlation between the fall of blood pressure and the inhibition of brain MAO suggests that the accumulation of amine in brain is responsible for the fall in pressure.3 Reactive oxygen species-mediated monocyte hypertrophy is prevented by pargyline at a concentration of 10 ?M.4 Formulations containing pargyline have been used to treat moderate hypertension.4,5
1.Fowler, C.J., Mantle, T.J., and Tipton, K.F.The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargylineBiochem. Pharmacol.31(22)3555-3561(1982) 2.Fuentes, J.A., Ordaz, A., and Neff, N.H.Central mediation of the antihypertensive effect of pargyline in spontaneously hypertensive ratsEur. J. Pharmacol.57(1)21-27(1979) 3.Yamori, Y., De Jong, W., Yamabe, H., et al.Effects of L-dopa and inhibitors of decarboxylase and monoamine oxidase on brain noradrenaline leves and blood pressure in spontaneously hypertensive ratsJ. Pharm. Pharmacol.24(9)690-695(1972) 4.Bianchi, P., Pimentel, D.R., Murphy, M.P., et al.A new hypertrophic mechanism of serotonin in cardiac myocytes: Receptor-independent ROS generationFASEB J.19(6)641-643(2005) 5.Puig, M., Wakade, A.R., and Kirpekar, S.M.Effect of the sympathetic nervous system of chronic treatment with parglyline and l-DOPAJ. Pharmacol. Exp. Ther.182(1)130-134(1972)
| Cas No. | 555-57-7 | SDF | |
| 别名 | 优降宁 | ||
| Canonical SMILES | C#CCN(C)CC1=CC=CC=C1 | ||
| 分子式 | C11H13N | 分子量 | 159.23 |
| 溶解度 | DMSO : 100 mg/mL (628.02 mM; Need ultrasonic) | 储存条件 | Store at -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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.2802 mL | 31.4011 mL | 62.8022 mL |
| 5 mM | 1.256 mL | 6.2802 mL | 12.5604 mL |
| 10 mM | 0.628 mL | 3.1401 mL | 6.2802 mL |
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| 给药剂量 | mg/kg |  |
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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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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Installation of Pargyline, a LSD1 Inhibitor, in the HDAC Inhibitory Template Culminated in the Identification of a Tractable Antiprostate Cancer Agent
J Med Chem 2021 Dec 23;64(24):17824-17845.PMID:34908406DOI:10.1021/acs.jmedchem.1c00966.
Pragmatic insertion of Pargyline, a LSD1 inhibitor, as a surface recognition part in the HDAC inhibitory pharmacophore was planned in pursuit of furnishing potent antiprostate cancer agents. Resultantly, compound 14 elicited magnificent cell growth inhibitory effects against the PC-3 and DU-145 cell lines and led to remarkable suppression of tumor growth in human prostate PC-3 and DU-145 xenograft nude mouse models. The outcome of the enzymatic assays ascertained that the substantial antiproliferative effects of compound 14 were mediated through HDAC6 isoform inhibition as well as selective MAO-A and LSD1 inhibition. Moreover, the signatory feature of LSD1 inhibition by 14 in the context of H3K4ME2 accumulation was clearly evident from the results of western blot analysis. Gratifyingly, hydroxamic acid 14 demonstrates good human hepatocytic stability and good oral bioavailability in rats and exhibits enough promise to emerge as a therapeutic for the treatment of prostate cancer in the near future.
Pargyline prevents MPTP-induced parkinsonism in primates
Science 1984 Sep 28;225(4669):1480-2.PMID:6332378DOI:10.1126/science.6332378.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin which produces permanent parkinsonism in human and nonhuman primates. Treatment of squirrel monkeys with Pargyline, a monoamine oxidase (MAO) inhibitor, prevents both clinical and neuropathological evidence of the neurotoxic effects of MPTP. Pargyline also inhibits conversion of MPTP to 1-methyl-4-phenylpyridinium ion (MPP+), a metabolic step that occurs rapidly after administration of MPTP in animals not treated with Pargyline. It is proposed that the conversion of MPTP to MPP+, possibly involving MAO, may be important for the neurotoxic effects of MPTP to take place, and MPTP itself may not be the neurotoxic agent.
Pargyline pretreatment prevents immunological changes induced by MPTP in mice
Immunopharmacology 1996 Nov;35(2):149-54.PMID:8956978DOI:10.1016/s0162-3109(96)00140-3.
The relationship between the central dopaminergic and the immune system is poorly understood. Experimental work suggest that damage of the nigrostriatal system may influence immunity. Immunological abnormalities have been described in Parkinson's disease and in a mouse model of this disorder induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this report, we present evidence that reduced numbers of L3T4 T cells in blood, and diminished primary antibody response to sheep erythrocytes in MPTP treated mice can be restored by Pargyline pretreatment. Since Pargyline prevents dopamine depletion in the striatum in MPTP treated animals, our data extend previous experimental observations and support a possible role for dopamine in immune regulation.
N-Methyl-benzylamine, a metabolite of Pargyline in man
Br J Clin Pharmacol 1979 Jun;7(6):595-8.PMID:465282DOI:10.1111/j.1365-2125.1979.tb04648.x.
1. N-methyl-benzylamine was identified in human urine and plasma after the administration of Pargyline in man. This metabolite was identified by thin layer chromatography mobility, gas chromatographic retention time and mass spectrum relative to authentic N-methyl-benzylamine. 2. [14C]-N-methyl-benzylamine, together with a small amount of [14C]-benzylamine, was formed in vitro from [14C]-pargyline when this was incubated with human and rat liver microsomes. 3. The urinary excretion rates of Pargyline and its metabolite have also been described.
Role of propiolaldehyde and other metabolites in the Pargyline inhibition of rat liver aldehyde dehydrogenase
Biochem Pharmacol 1986 May 1;35(9):1481-9.PMID:3707613DOI:10.1016/0006-2952(86)90113-9.
The metabolism of Pargyline proceeds by way of three separate cytochrome P-450 catalyzed N-dealkylation reactions: N-depropargylation, N-demethylation and N-debenzylation. Propiolaldehyde, a product of N-depropargylation, is a potent inhibitor of aldehyde dehydrogenase (AlDH). The formation of pargyline-derived propiolaldehyde by isolated rat liver microsomes in vitro was confirmed using gas chromatographic/mass spectrometric techniques. The measured rates of propiolaldehyde formation for uninduced and phenobarbital-induced microsomes in vitro were 0.2 +/- 0.03 and 0.9 +/- 0.2 mumole/30 min/g wet weight liver respectively. However, these rates may have been artificially low due to competition between semicarbazide, the trapping agent, and microsomal proteins for the generated propiolaldehyde. CO significantly inhibited the microsome-catalyzed N-depropargylation reaction in vitro, whereas CoCl2 pretreatment of rats partially blocked the pargyline-induced rise in blood acetaldehyde after ethanol. Inhibition of the low Km liver mitochondrial AlDH by propiolaldehyde in vitro exhibited first-order kinetics, which is consistent with irreversible inhibition. Acetaldehyde did not attenuate the inhibition of AlDH by propiolaldehyde in vitro or by Pargyline in vivo. Propargyl alcohol, a substance which is metabolized to propiolaldehyde by alcohol dehydrogenase, also inhibited AlDH in vivo and caused a quantitatively similar rise in blood acetaldehyde after ethanol as Pargyline. Other putative metabolites of Pargyline, namely benzylamine and propargylamine, inhibited AlDH in vivo, albeit to a lesser degree than Pargyline, but neither of these amines inhibited AlDH directly. Monoamine oxidase was implicated in the conversion of benzylamine to an active inhibitory species, possibly an imine. From these studies, we conclude that propiolaldehyde was the primary metabolite responsible for the Pargyline inhibition of AlDH in vivo; however, certain amine metabolites may have contributed to a lesser degree by conversion to yet unknown inhibitory forms.