Norcocaine (hydrochloride)
(Synonyms: 去甲可卡因盐酸盐溶液) 目录号 : GC46186
An Analytical Reference Standard
Cas No.:61585-22-6
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
Norcocaine (hydrochloride) is an analytical reference standard categorized as a metabolite of cocaine .1,2,3 This product is intended for research and forensic applications.
|1. Kolbrich, E.A., Barnes, A.J., Gorelick.D.A., et al. Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration. J. Anal. Toxicol. 30(8), 501-510 (2006).|2. Hawks, R.L., Kopin, I.J., Colburn, R.W., et al. Norcocaine: A pharmacologically active metabolite of cocaine found in brain. Life Sci. 15(12), 2189-2195 (1974).|3. Misra, A.L., Nayak, P.K., Bloch, R., et al. Estimation and disposition of [3H]benzoylecgonine and pharmacological activity of some cocaine metabolites. J. Pharm. Pharmacol. 27(10), 784-786 (1975).
| Cas No. | 61585-22-6 | SDF | |
| 别名 | 去甲可卡因盐酸盐溶液 | ||
| Canonical SMILES | O=C(C1=CC=CC=C1)O[C@H]2C[C@@H]3CC[C@@H](N3)[C@H]2C(OC)=O.Cl | ||
| 分子式 | C16H19NO4 • HCl | 分子量 | 325.8 |
| 溶解度 | Ethanol: 300 mg/ml,Water: 2.5g/L | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.0694 mL | 15.3468 mL | 30.6937 mL |
| 5 mM | 0.6139 mL | 3.0694 mL | 6.1387 mL |
| 10 mM | 0.3069 mL | 1.5347 mL | 3.0694 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern
Toxins (Basel) 2022 Apr 13;14(4):278.PMID:35448887DOI:10.3390/toxins14040278.
Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or 'crack' cocaine, the free base. While the first is commonly administered by insufflation ('snorting') or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, Norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine's prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.
Metabolism of Norcocaine, N-hydroxy Norcocaine and cocaine-N-oxide in the rat
Xenobiotica 1979 Mar;9(3):189-99.PMID:473794DOI:10.3109/00498257909038720.
1. The metabolism of [3H]Norcocaine, N-hydroxy[3H]Norcocaine and cocaine-N-oxide has been investigated in rats after i.v. injection. 2. The biological t 1/2 of Norcocaine (dose 2 mg/kg i.v.) in plasma, liver and brain were 0.4, 1.6, 0.5 h, respectively and the compound was not detectable in the central nervous system 6 h after injection. The % dose of Norcocaine excreted unchanged in urine and faeces in 96 h were 0.7 and 1.0, respectively. Benzoylnorecgonine, norecgonine, norecgonine methyl ester and an unidentified compound were excreted in urine. 3. The biological t 1/2 of N-hydroxynorcocaine (5 mg/kg i.v.) in brain and plasma were 0.3, 1.6 h respectively and only 1.3 and 1.6% of dose were excreted unchanged in urine and faeces in 96 h. N-Hydroxybenzoylnorecgonine and N-hydroxynorecgonine methyl ester were the major urinary metabolites. N-hydroxynorcocaine was not metabolized to Norcocaine in vitro by liver microsomes. Doses of greater than 7.5 mg/kg i.v. resulted in death of rats by cardiorespiratory arrest. 4. Cocaine-N-oxide (50 mg/kg i.v.) yielded ecgonine-N-oxide methyl ester as its major metabolite; other minor metabolites were cocaine (0.5%), Norcocaine (1%), benzoylecgonine, ecgonine, ecgonine-N-oxide, along with minor amounts of unmetabolized compound. Lethality of cocaine-N-oxide (100 mg/kg i.v.) was possibly due to metabolism to Norcocaine and cocaine.
Liver toxicity from Norcocaine nitroxide, an N-oxidative metabolite of cocaine
J Pharmacol Exp Ther 1998 Jan;284(1):413-9.PMID:9435205doi
The oxidative metabolism of cocaine to Norcocaine nitroxide has been postulated to be essential for cocaine hepatotoxicity. The hepatic effects of Norcocaine nitroxide have never been evaluated in vivo, however. In this study mice were administered Norcocaine nitroxide i.p., and hepatotoxicity was assessed using serum alanine aminotransferase activities and microscopic examination of liver tissue. Hepatotoxicity of Norcocaine nitroxide was dose-related; significant injury was detectable at doses of 20 to 30 mg/kg i.p., and severe hepatocellular necrosis was observed at doses of 40 and 50 mg/kg. Elevated serum alanine aminotransferase activities peaked between 12 and 18 hr after Norcocaine nitroxide treatment. Electron microscopy revealed the presence of pronounced changes in cell morphology as early as 30 min after the Norcocaine nitroxide dose. Pretreatment of mice with phenobarbital had no effect on the magnitude of hepatic injury but shifted the intralobular site of necrosis from the midzonal to the periportal region. Pretreatment with diazinon, an esterase inhibitor, increased Norcocaine nitroxide-induced liver damage, whereas each of the P450 inhibitors SKF 525A, cimetidine, troleandomycin, ketaconazole and chloramphenicol significantly diminished Norcocaine nitroxide hepatotoxicity. The results indicate that Norcocaine nitroxide is hepatotoxic and suggest the involvement of P450 enzymes.
Kinetic characteristics of Norcocaine N-hydroxylation in mouse and human liver microsomes: involvement of CYP enzymes
Arch Toxicol 2000 Nov;74(9):511-20.PMID:11131030DOI:10.1007/s002040000154.
The first step in the oxidative metabolism of cocaine is N-demethylation to Norcocaine, which is further N-hydroxylated to more toxic N-hydroxynorcocaine. In this study we examined the kinetics of Norcocaine N-hydroxylation mediated by cytochrome P450 (CYP) in mouse and human liver microsomes. N-hydroxynorcocaine was identified by analytical HPLC-MS after incubation of Norcocaine with mouse liver microsomes in the presence of NADPH. In mouse liver microsomes, there was no apparent difference in Km values for Norcocaine N-hydroxylation between male and female microsomes, while the Vmax rate was approximately two times higher in female than in male microsomes (34+/-10 v. 16+/-4 pmol/min per mg protein). The Km value for Norcocaine N-hydroxylation in human liver microsomes was approximately three times higher than that observed in comparable incubations using mouse liver microsomes, whereas the Vmax rate was ten times lower. Both cocaine and Norcocaine induced type I difference spectra upon interaction with CYP in mouse liver microsomes. In contrast, in human microsomes both type I and type II spectra were recorded. In the 0.01 to 1 mM concentration range, cocaine and Norcocaine inhibited mouse microsomal testosterone 6alpha-, 7alpha- and 16alpha-hydroxylation reactions by 20% to 30%. Testosterone 6beta- and 15alpha-hydroxylations were blocked by 60% and 50%, respectively, by 1 mM Norcocaine, while only 40% inhibition was obtained with 1 mM cocaine. Coumarin 7-hydroxylation and pentoxyresorufin O-deethylation were inhibited by 50% by 1 and 0.4 mM Norcocaine, respectively. In contrast, 10 and 2 mM cocaine, respectively, were needed to obtain the same degrees of inhibition. In human liver microsomes, 1 mM Norcocaine and cocaine blocked testosterone 6beta-hydroxylase by 60% and 40%, respectively. Coumarin 7-hydroxylation was inhibited by only 30% by Norcocaine (5.4 mM) and cocaine (10 mM). Norcocaine N-hydroxylation in mouse and human liver microsomes was blocked by 30% and 60%, respectively, by alpha-naphthoflavone (0.1 mM). The reaction was inhibited by 30-40% by metyrapone, cimetidine and gestodene at a concentration of 1 mM in mouse microsomes, while in human microsomes, 70% inhibition was obtained with 1 mM metyrapone and cimetidine. Taken together, these results indicate that (1) Norcocaine N-hydroxylation is at least partly a CYP-mediated reaction, (2) the rate of reaction is considerably lower in human liver microsomes than in mouse liver microsomes and (3) several CYP subfamilies including 1A, 2A, 3A and possibly 2B may contribute to the formation of N-hydroxynorcocaine.
Norcocaine is a potent modulator of haemodynamic responses, plasma catecholamines and cardiac hormone release in conscious rats
Toxicology 1998 Jul 3;128(2):101-11.PMID:9710151DOI:10.1016/s0300-483x(98)00053-5.
We examined the effects of intravenously administered cocaine and Norcocaine on the haemodynamics, the plasma immunoreactive atrial natriuretic peptide (ANP), the N-terminal peptide of proANP (NT-ANP) and the plasma catecholamine levels in conscious, chronically cannulated Sprague-Dawley rats. Cocaine caused an immediate significant peak rise in the mean arterial pressure which was followed by a dose-dependent sustained pressor response. Cocaine also decreased the heart rate and increased the right atrial pressure. Norcocaine at a dose of 1 mg/kg maximally decreased the heart rate which did not recover to the basal level within 15 min. Norcocaine (1 mg/kg) did not affect the right atrial pressure but with a dose of 3 mg/kg an elevation of 2.2 +/- 0.3 mmHg (P < 0.005) was observed which did not recover to the control level during the 30 min study period. Plasma immunoreactive ANP and NT-ANP levels increased significantly in a dose-dependent manner after the injection of cocaine. Norcocaine treatments also resulted in significant correlations between ANP or NT-ANP levels and haemodynamic variables, especially between the right atrial pressure and the plasma immunoreactive ANP levels (r = 0.58, n = 28, P < 0.005). Cocaine and Norcocaine enhanced the plasma adrenaline levels but Norcocaine, already at a dose of 1 mg/kg, caused a maximal increase in the plasma adrenaline levels. The long lasting increase in the right atrial pressure after Norcocaine and the decrease in the heart rate after higher doses of cocaine suggest the role for this metabolite, or a further metabolite of Norcocaine, in the cardiovascular and haemodynamic responses to cocaine seen in conscious rats.