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1,4-Diaminobutane-d8 dihydrochloride

(Synonyms: 1,4-二氨基丁烷二盐酸盐-d8) 目录号 : GC68486

1,4-Diaminobutane-d8 dihydrochloride是氘取代的1,4-Diaminobutane dihydrochloride,它更稳定,在药物开发过程中主要用作定量示踪剂。

1,4-Diaminobutane-d8 dihydrochloride Chemical Structure

Cas No.:284665-22-1

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5mg
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10mg
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25mg
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Sample solution is provided at 25 µL, 10mM.

Description

1,4-Diaminobutane-d8 dihydrochloride is the deuterium-substituted 1,4-Diaminobutane dihydrochloride, which is more stable and largely as tracer for quantitation during the drug development process[1]. 1,4-Diaminobutane-d8 dihydrochloride is an endogenous metabolite, acts as an indicator of pollution-induced stress in higher plants[2]. 1,4-Diaminobutane-d8 dihydrochloride can be used as an internal standard in LC-MS/MS for the quantification of polyamines in biological samples[3].

1,4-Diaminobutane-d8 dihydrochloride (100-1000μM; 24h) promotes the growth of CT-26 tumor cells[4]. 1,4-Diaminobutane-d8 dihydrochloride (0-50mM; 2h) protected against oxidative stress induced by polymyxin B (PmB; 1mg/ml) in Burkholderia cenocepacia, resulted in increased ROS generation and a parallel increased sensitivity to PmB[5].

1,4-Diaminobutane-d8 dihydrochloride (0.1-100mg/kg; i.p. ; 30min) significantly decreased the immobility time in mice in the forced swimming test (FST), which produces a antidepressant-like effect[6]. 1,4-Diaminobutane-d8 dihydrochloride (200-400mg/kg; i.p. ; 30, 60, 90, 120, 150, 180, 210 and 240min) has dose dependent analgesic activity in rats in hot plate test (55.5±0.1℃), to which tolerance develops[7].

References:
[1] RUSSAK E M, BEDNARCZYK E M. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals [J]. Ann Pharmacother, 2019, 53(2): 211-6.
[2] SEQUERRA E B, GARDINO P, HEDIN-PEREIRA C, et al. Putrescine as an important source of GABA in the postnatal rat subventricular zone [J]. Neuroscience, 2007, 146(2): 489-93.
[3] HAKKINEN M R, ROINE A, AURIOLA S, et al. Analysis of free, mono- and diacetylated polyamines from human urine by LC-MS/MS [J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2013, 941(81-9.
[4] FARRIOL M, SEGOVIA-SILVESTRE T, CASTELLANOS J M, et al. Role of putrescine in cell proliferation in a colon carcinoma cell line [J]. Nutrition, 2001, 17(11-12): 934-8.
[5] EL-HALFAWY O M, VALVANO M A. Putrescine reduces antibiotic-induced oxidative stress as a mechanism of modulation of antibiotic resistance in Burkholderia cenocepacia [J]. Antimicrob Agents Chemother, 2014, 58(7): 4162-71.
[6] ZOMKOWSKI A D, SANTOS A R, RODRIGUES A L. Putrescine produces antidepressant-like effects in the forced swimming test and in the tail suspension test in mice [J]. Prog Neuropsychopharmacol Biol Psychiatry, 2006, 30(8): 1419-25.
[7] GENEDANI S, PICCININI G, BERTOLINI A. Putrescine has analgesic activity, in rats [J]. Life Sci, 1984, 34(24): 2407-12.

1,4-Diaminobutane-d8 dihydrochloride是氘取代的1,4-Diaminobutane dihydrochloride,它更稳定,在药物开发过程中主要用作定量示踪剂[1]。1,4-Diaminobutane-d8 dihydrochloride是一种内源代谢物,在高等植物中作为污染诱导胁迫的指示物[2]。1,4-Diaminobutane-d8 dihydrochloride可作为LC-MS/MS定量生物样品中多胺的内标定物[3]

1,4-Diaminobutane-d8 dihydrochloride(100-1000μM; 24h)促进CT-26肿瘤细胞生长[4]。1,4-Diaminobutane-d8 dihydrochloride(0-50mM; 2h)对多粘菌素B(PmB, 1mg/ml)诱导的洋葱伯克霍尔德菌的氧化应激有保护作用,导致ROS生成增加,同时对PmB的敏感性增加[5]

使用1,4-Diaminobutane-d8 dihydrochloride (0.1-100mg/kg; i.p; 30min)处理小鼠,1,4-Diaminobutane-d8 dihydrochloride显著减少小鼠在FST(forced swimming test,强迫游泳试验)中的静止时间,产生抗抑郁样作用[6]。使用1,4-Diaminobutane-d8 dihydrochloride(200-400mg/kg; i.p. ; 30, 60, 90, 120, 150, 180, 210 and 240min)处理进行55.5±0.1℃热板实验的大鼠,1,4-Diaminobutane-d8 dihydrochloride对大鼠有剂量依赖性镇痛活性,并产生耐受[7]

实验参考方法

Cell experiment [1]:

Cell lines

Burkholderia cenocepacia

Preparation Method

Bacteria grew in LB at 37℃. Polymyxin B (PmB, 1mg/ml) was diluted in 0.2% bovine serum albumin-0.01% glacial acetic acid buffer. Overnight cultures of the parental Burkholderia cenocepacia in LB medium were diluted to an optical density at 600nm (OD600) of 0.1 in fresh medium. Five-milliliter aliquots were incubated at 37°C for 3h at 200rpm. 1,4-Diaminobutane-d8 dihydrochloride was added at the specified concentrations, and the cultures were further incubated at 37°C for 2h at 200rpm. After incubation, the OD600 was measured, and aliquots containing cells equivalent to an OD600 of 0.4 were pelleted, washed with phosphate buffered saline (PBS), and resuspended in 1ml of PBS. Superoxide radicals and other ROS were determined by diluting the obtained suspension 100 fold in 1ml PBS and adding 2’,7’-dichlorofluorescein diacetate (DCF) to a final concentration of 2μM. The reaction mixture was then incubated at 37°C for 30min with rotation. After incubation, the fluorescence was measured in 200μl aliquots placed into 96 well white plates at excitation of 480nm and emission of 521nm. In addition, the OD600s of the same suspensions were measured and used to normalize the fluorescence values.

Reaction Conditions

0-50mM; 2h

Applications

1,4-Diaminobutane-d8 dihydrochloride protected against oxidative stress induced by polymyxin B (PmB) in Burkholderia cenocepacia, resulted in increased ROS generation and a parallel increased sensitivity to PmB.
Animal experiment [2]:

Animal models

Swiss mice

Preparation Method

Swiss mice of either sex (30-40g) were maintained at 22-27℃ with free access to water and food, under a 12:12h light/dark cycle. The forced swimming test (FST) was carried out in mice individually forced to swim in an open cylindrical container (diameter 10cm, height 25cm), containing 19cm of water at 25±1℃; the total duration of immobility during the 6min test. Each mouse was judged to be immobile when it ceased struggling and remained floating motionless in the water, making only those movements necessary to keep its head above water. In order to investigate the antidepressant-like effect of the putrescine, it was administered 1,4-Diaminobutane-d8 dihydrochloride (dose range: 0.1-100mg/kg; i.p. ) 30 min before the FST.

Dosage form

0.1-100mg/kg; i.p. ; 30min

Applications

1,4-Diaminobutane-d8 dihydrochloride significantly decreased the immobility time in the forced swimming test (FST), which produces a antidepressant-like effect.

References:
[1] EL-HALFAWY O M, VALVANO M A. Putrescine reduces antibiotic-induced oxidative stress as a mechanism of modulation of antibiotic resistance in Burkholderia cenocepacia [J]. Antimicrob Agents Chemother, 2014, 58(7): 4162-71.
[2] ZOMKOWSKI A D, SANTOS A R, RODRIGUES A L. Putrescine produces antidepressant-like effects in the forced swimming test and in the tail suspension test in mice [J]. Prog Neuropsychopharmacol Biol Psychiatry, 2006, 30(8): 1419-25.

化学性质

Cas No. 284665-22-1 SDF Download SDF
别名 1,4-二氨基丁烷二盐酸盐-d8
分子式 C4H6D8Cl2N2 分子量 169.12
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1 mM 5.913 mL 29.5648 mL 59.1296 mL
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