(-)-Physostigmine (salicylate)
(Synonyms: 水杨酸毒扁豆碱; Eserine salicylate) 目录号 : GC48551
An alkaloid and cholinergic agent
Cas No.:57-64-7
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
(-)-Physostigmine is an alkaloid that has been found in Calabar beans and a cholinergic agent.1,2 It inhibits acetylcholinesterase (AChE; IC50 = 0.67 nM).2 (-)-Physostigmine (10 µM) inhibits ChE and increases vagal stimulation-induced ACh output in isolated chicken heart.3 In vivo, (-)-physostigmine (200 and 400 µg/kg) induces decentralized lower eyelid contractions and increases blood pressure in anesthetized rats.4
1.Proudfoot, A.The early toxicology of physostigmine: a tale of beans, great men and egosToxicol. Rev.25(2)99-138(2006) 2.Ogura, H., Kosasa, T., Kuriya, Y., et al.Comparison of inhibitory activities of donepezil and other cholinesterase inhibitors on acetylcholinesterase and butyrylcholinesterase in vitroMethods Find. Exp. Clin. Pharmacol.22(8)609-613(2000) 3.Dieterich, H.A., Kaffel, H., Kilbinger, H., et al.The effects of physostigmine on cholinesterase activity, storage and release of acetylcholine in the isolated chicken heartJ. Pharmacol. Exp. Ther.199(1)236-246(1976) 4.SzeberÉnyi, J., Varga, A., PongrÁcz, M.F., et al.Centrally mediated contraction of the lower eyelid elicited by anticholinesterases in anaesthetized ratsJ. Pharm. Pharmacol.24(1)85-86(1972)
| Cas No. | 57-64-7 | SDF | |
| 别名 | 水杨酸毒扁豆碱; Eserine salicylate | ||
| Canonical SMILES | CNC(OC1=CC([C@@](CCN2C)(C)[C@@]2([H])N3C)=C3C=C1)=O.OC(C4=C(O)C=CC=C4)=O | ||
| 分子式 | C15H21N3O2•C7H6O3 | 分子量 | 413.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 10 mg/ml,Ethanol: 1 mg/ml,PBS (pH 7.2): 1 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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| 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 | 2.4184 mL | 12.0919 mL | 24.1838 mL |
| 5 mM | 0.4837 mL | 2.4184 mL | 4.8368 mL |
| 10 mM | 0.2418 mL | 1.2092 mL | 2.4184 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。
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Physostigmine salicylate as an antidote
Int J Clin Pharmacol Ther Toxicol 1980 Dec;18(12):523-35.PMID:7228447doi
Most poisonings with anticholinergics deal with simple cases without diagnostic or therapeutic difficulties; however, in difficult or unclarified cases a new method for diagnosis and treatment is the antidote physostigmine salicylate. Within 15 minutes after application of 2 mg of the antidote the central anticholinergic symptoms disappear, such as respiratory depression, coma, cramps and hallucinations as do the peripheral anticholinergic symptoms as cardiac rhythm disturbance, dry mouth and red dry skin. No fatal overdose with anticholinergic drugs occurs if the antidote is given in time.
Kinetics of transdermal penetration of an organic ion pair: physostigmine salicylate
J Pharm Sci 1992 Oct;81(10):990-5.PMID:1432625DOI:10.1002/jps.2600811006.
Physostigmine salicylate was delivered from a series of solvents consisting of isopropyl myristate, isopropyl alcohol (IPA), and their mixtures across dermatomed human skin. The apparent steady-state fluxes over the time range of the test, obtained separately for physostigmine and its corresponding salicylate, indicate a consistent trend toward higher values for the salicylate in the series tested. The ratios of salicylate fluxes to physostigmine fluxes ranged from 1.1 to 3.34, the higher ratios being obtained at a volume fraction of IPA exceeding 0.7. Ionization of the ion pair at the pH of the hydrated stratum corneum immediately after its partitioning into the membrane, followed by differential diffusion of the species across the membrane, is consistent with the kinetics of penetration. It is proposed that the apparent volume of distribution of physostigmine is larger than that of salicylate and, hence, a smaller concentration difference across the diffusion barrier exists for physostigmine. This hypothesis can explain the lower flux of physostigmine to conform to Fick's first law of diffusion and the assumption of equal molar transfer to the skin of both species. The hypothesis implies that if steady state appears to have been reached for the faster migrating salicylate over the time range tested then the apparent steady state of physostigmine is not a true one. Increasing the salicylate content in one of the donor solutions by eight times over that of physostigmine decreased the saturation concentration of physostigmine but not in its flux. Increasing the physostigmine content by 6.5 times over that of salicylate in the same donor solution did not change either the flux or the salicylate concentration but decreased the permeability coefficient of physostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)
Physostigmine antagonizes ketamine
Anesth Analg 1980 Oct;59(10):764-7.PMID:6999946doi
In a random cross-over double-blind trial, the effects of intravenous physostigmine salicylate (2.0 mg) and placebo were observed in seven healthy volunteers 10 minutes after the intravenous administration of 1.5 mg/kg of ketamine. Recovery time was significantly shorter after physostigmine than after placebo. Nystagmus and blurred vision, which followed ketamine anesthesia, disappeared more rapidly when physostigmine was given. This study confirms previous observations that physostigmine counteracts some of the manifestation of ketamine aftereffects which resemble the so-called central anticholinergic syndrome. Nausea and vomiting were significantly more frequent after physostigmine administration.
Physostigmine in mania
Arch Gen Psychiatry 1978 Jan;35(1):119-22.PMID:339869DOI:10.1001/archpsyc.1978.01770250121012.
Seven men and one woman with primary affective disorder, mania, were given a slow intravenous infusion of physostigmine salicylate. In six patients, mood and thought content changed from mania toward depression as evaluated by either a visual analog mood scale or the Pettersen scale. Two other patients, who were the only predominantly irritable manics in the study, demonstrated little change in their hostility, although one became somewhat depressed. These findings are consistent with earlier reports of suppression of manic symptoms after physostigmine infusion in some but not all patients with mania. The pharmacologic mechanism of physostigmine reversal of manic symptoms may be the direct result of increased cholinergic activity or a result of the effect of increased cholinergic activity on other brain neurotransmitters.
Physostigmine for Alzheimer's disease
Cochrane Database Syst Rev 2001;2001(2):CD001499.PMID:11405996DOI:10.1002/14651858.CD001499.
Background: The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly by inhibiting acetylcholinesterase (AChE), the enzyme that destroys acetylcholine after it has been secreted into the synaptic clefts. Physostigmine is an AChE inhibitor originally extracted from calabar beans. It is licensed in many countries as an agent for reversing the effect of drugs and poisons causing the anticholinergic syndrome. Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half-life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled-release (CR) oral formulation, and a skin patch. It has been proposed as a potential drug for the symptomatic treatment of AD. Objectives: To determine whether there is evidence of beneficial effects for the use of physostigmine in Alzheimer's disease. To assess the incidence and severity of adverse effects. Search strategy: The Cochrane Controlled Trials Register was searched using the following terms: 'physostigmine', 'physostigmine salicylate', 'Synapton' and 'Antilirium' in accordance with the Cochrane Dementia and Cognitive Improvement Group's search strategy. The pharmaceutical company was contacted. Selection criteria: All relevant unconfounded, double-blind, randomized, placebo-controlled trials in which physostigmine was administered for more than one day to patients with dementia of Alzheimer type. Trials in which the allocation to the treatment was not randomized, or in which the allocation to the treatment was not concealed were excluded. Data collection and analysis: Data were extracted independently by two reviewers (JMC & JB), pooled where appropriate and possible, and the weighted or standardized mean differences or Peto odds ratios (95% CI) were estimated. Where possible, intention-to-treat analysis was used. Main results: Fifteen studies were included using four different methods of administration of physostigmine. Four studies, involving 29 people in total, used intravenous infusion; seven, involving 131 people, used a conventional oral form; four, involving 1456 participants, used a controlled-release oral form, and one study of 181 people used a verum skin patch. There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo. The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59, 13.54) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. The best dose physostigmine (mean 27mg/day) was associated with a 2.0 point improvement on ADAS-Cog score (mean difference -2.02, 95% confidence interval -3.59, -0.45 on an intention to treat basis) compared with placebo at 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% confidence limits 1.15, 8.07) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% confidence limits 3.17, 7.33), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%confidence limits 4.29, 9.95) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming compared with placebo at 24 weeks. The results from the study of the verum patch physostigmine show that the double dose (delivering mean dose 12mg/day) was associated with statistically significantly higher numbers suffering at least one adverse event of vomiting, nausea or abdominal cramps compared with placebo at 24 weeks, but placebo was associated with statistically significantly greater numbers of gastrointestinal complaints at 24 weeks compared with single-dose physostigmine. Reviewers' conclusions: The evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease is limited. Even in a controlled release formulation designed to overcome the short half-life, physostigmine showed no convincing benefit and adverse effects remained common leading to a high rate of withdrawal.