Lidocaine CAS 137-58-6
Introduction：Basic information about Lidocaine CAS 137-58-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Lidocaine Basic informationdescription Chemical property Uses
| Product Name: | Lidocaine |
| Synonyms: | 2-(Diethylamino)-2',6'-acetoxylidide;2-(diethylamino)-2’,6’-acetoxylidide;2-(diethylamino)-n-(2,6-dimethylphenyl)-acetamid;2',6'-Acetoxylidide, 2-(diethylamino)-;6’-acetoxylidide,2-(diethylamino)-2;Acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-;Ligoncaine;Maricaine |
| CAS: | 137-58-6 |
| MF: | C14H22N2O |
| MW: | 234.34 |
| EINECS: | 205-302-8 |
| Product Categories: | Halogenated Heterocycles;Pharma materials;API;REGITINE;Other APIs;Alphacaine, Xylocaine, lignocaine;Research Chemical;137-58-6 |
| Mol File: | 137-58-6.mol |
Lidocaine Chemical Properties
| Melting point | 66-69°C |
| Boiling point | bp4 180-182°; bp2 159-160° |
| density | 0.9944 (rough estimate) |
| refractive index | 1.5110 (estimate) |
| Fp | 9℃ |
| storage temp. | Store at RT |
| solubility | ethanol: 4 mg/mL |
| pka | pKa 7.88(H2O)(Approximate) |
| form | powder |
| color | White to slightly yellow |
| Water Solubility | practically insoluble |
| Merck | 14,5482 |
| BCS Class | 1 |
| Stability: | Stable. Incompatible with strong oxidizing agents. |
| Major Application | cleaning products cosmetics food and beverages personal care pharmaceutical (small molecule) |
| Cosmetics Ingredients Functions | NOT REPORTED |
| InChI | 1S/C14H22N2O/c1-5-16(6-2)10-13(17)15-14-11(3)8-7-9-12(14)4/h7-9H,5-6,10H2,1-4H3,(H,15,17) |
| InChIKey | NNJVILVZKWQKPM-UHFFFAOYSA-N |
| SMILES | CCN(CC)CC(=O)Nc1c(C)cccc1C |
| LogP | 2.440 |
| CAS DataBase Reference | 137-58-6(CAS DataBase Reference) |
| NIST Chemistry Reference | Lidocaine(137-58-6) |
| EPA Substance Registry System | Acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)- (137-58-6) |
Safety Information
| Hazard Codes | Xn,T,F |
| Risk Statements | 22-39/23/24/25-23/24/25-11 |
| Safety Statements | 22-26-36-45-36/37-16-7 |
| RIDADR | 3249 |
| WGK Germany | 3 |
| RTECS | AN7525000 |
| TSCA | TSCA listed |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| HS Code | 29242990 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral |
| Hazardous Substances Data | 137-58-6(Hazardous Substances Data) |
| Toxicity | LD50 oral in rat: 317mg/kg |
| description | Lidocaine is a local anesthetic, also known as Xylocaine, in recent years it has been replaced procaine, widely used in local infiltration anesthesia in cosmetic plastic surgery, it can block the nerve excitability and conduction by inhibiting the sodium channels of nerve cell membrane. The fat soluble and protein binding rate of lidocaine is higher than procaine, its cell penetrating ability is strong, fast onset, long duration of action, the interaction strength is 4 times of procaine. Lidocaine is used in infiltration anesthesia, epidural anesthesia, topical anesthesia (including thoracoscopy or abdominal surgery for mucosal anesthesia) and nerve block. In order to extend the time of anesthesia, reduce the poisoning of lidocaine and other side effects, can be added in the anesthetic epinephrine. Lidocaine can also be used for the treatment of ventricular premature beat after acute myocardial infarction, ventricular tachycardia, digitalis poisoning, cardiac surgery and cardiac catheterization-induced ventricular arrhythmias, including ventricular premature beats, ventricular tachycardia and ventricular fibrillation. Lidocaine is also used for duration status of epilepsy which other anti-seizure drugs are not effective, as well as local or spinal anesthesia. But it is usually ineffective for supraventricular arrhythmias. |
| Chemical property | Lidocaine is white needle like crystals, and its melting point is 68-69℃; boiling point is 180-182℃ (0.53kPa), soluble in ethanol in 159-160℃ (0.267kPa), ether, benzene, chloroform and oil, do not dissolve in water. In common use radical hydrochloride, lidocaine hydrochloride (C14H22N2O • HCL, [73-78-9]) is a white crystalline powder. Melting point 127-129℃, and the monohydrate melting point is 77-78℃. Easily soluble in water, 0.5% aqueous solution pHO 4.0-5.5. Odorless, bitter taste. |
| Uses | Lidocaine is an Anesthetic (local); antiarrhythmic (class IB). Long-acting, membrane stabilizing agent against ventricular arrhythmia. Originally developed as a local anesthetic. Neuroprotective & Neuroresearch Products. Lidocaine is widely used in surface anesthesia, anesthesia, conduction anesthesia and epidural anesthesia. The LD50 of oral lidocaine hydrochloride to mice was 290 mg/kg. |
| Description | Lidocaine [2-(diethylamino)-N-(2, 6-dimethylphenyl) acetamide monohydrochloride] is the mostcommonly used amino amide-type local anesthetic. Lidocaine is very lipid soluble and, thus, hasa more rapid onset and a longer duration of action than most amino ester-type local anesthetics,such as procaine and tetracaine. It can be administered parenterally (with or without epinephrine)or topically either by itself or in combination with prilocaine or etidocaine as a eutectic mixturethat is very popular with pediatric patients. The use of lidocaine–epinephrine mixtures should beavoided, however, in areas with limited vascular supply to prevent tissue necrosis. Lidocaine alsofrequently is used as a class IB antiarrhythmic agent for the treatment of ventricular arrhythmias,both because it binds and inhibits sodium channels in the cardiac muscle and because of itslonger duration of action than amino ester-type local anesthetics. Central nervous system changes are the most frequently observed systemic toxicities oflidocaine. The initial manifestations are restlessness, vertigo, tinnitus, slurred speech, andeventually, seizures. Subsequent manifestations include CNS depression with a cessation ofconvulsions and the onset of unconsciousness and respiratory depression or cardiac arrest. Thisbiphasic effect occurs because local anesthetics initially block the inhibitory GABAergicpathways, resulting in stimulation, and eventually block both inhibitory and excitatory pathways (i.e., block the sodium channels associated with the NMDA receptors, resulting in overall CNS inhibition). |
| Chemical Properties | solid |
| Originator | Xylocaine,Astra,US,1949 |
| Uses | Lidocaine is used in creams and lotions to soothe areas of inflamed skin or for example in hemorrhoid preparations to reduce discomfort; used bydoctors to anesthetise areas prior to surgery, often avoiding the need for a general anesthetie; used by injection after a heart attack to treat some rhythm disturbances. |
| Uses | Lidocaine (Alphacaine)is a selective inverse peripheral histamine H1-receptor agonist with an IC50 of >32 μM. [1] Histamine is responsible for many features of allergic reactions. Lidocaine (Alphacaine)is a second-generation antihistamine agent closely st |
| Uses | Antiarrhythmic Agents, Anesthetics；Anticonvulsant；antihypertensive |
| Definition | ChEBI: Lidocaine is the monocarboxylic acid amide resulting from the formal condensation of N,N-diethylglycine with 2,6-dimethylaniline. It has a role as a local anaesthetic, an anti-arrhythmia drug, an environmental contaminant, a xenobiotic and a drug allergen. It is a monocarboxylic acid amide, a tertiary amino compound and a member of benzenes. It derives from a glycinamide. |
| Indications | Experimentally, lidocaine has been found to prevent VF arising during myocardial ischemia or infarction by preventing the fragmentation of organized largewavefronts into heterogeneous wavelets. Although lidocaine is of proven benefit in preventing VF early after clinical myocardial infarction, there is no evidence that it reduces mortality. To the contrary, lidocaine may increase mortality after myocardial infarction by approximately 40% to 60%.There are no controlled studies of lidocaine in secondary prevention of recurrence of VT or VF. Lidocaine terminates organized monomorphic spontaneous VT or induced sustained VT in only approximately 20% of cases and is less effective than many other antiarrhythmic drugs. In a blinded, randomized study of intravenous lidocaine versus intravenous amiodarone in out-of-hospital VF resistant to defibrillation, lidocaine was associated with half the likelihood of survival to hospital admission compared with amiodarone. |
| Manufacturing Process | One mol of 2,6-xylidine is dissolved in 800 ml glacial acetic acid. The mixtureis cooled to 10°C, after which 1.1 mol chloracetyl chloride is added at onetime. The mixture is stirred vigorously during a few moments after which1,000 ml half-saturated sodium acetate solution, or other buffering oralkalizing substance, is added at one time. The reaction mixture is shakenduring half an hour. The precipitate formed which consists of ω-chloro-2,6-dimethyl-acetanilide is filtered off, washed with water and dried. The productis sufficiently pure for further treatment. The yield amounts to 70 to 80% ofthe theoretical amount. One mole of the chloracetyl xylidide thus prepared and 2.5 to 3 mols diethylamine are dissolved in 1,000 ml dry benzene. The mixture is refluxed for 4 to5 hours. The separated diethyl amine hydrochloride is filtered off. The benzenesolution is shaken out two times with 3N hydrochloric acid, the first time with800 ml and the second time with 400 ml acid. To the combined acid extractsis added an approximately 30% solution of sodium hydroxide until theprecipitate does not increase. The precipitate, which sometimes is an oil, is taken up in ether. The ethersolution is dried with anhydrous potassium carbonate after which the ether isdriven off. The remaining crude substance is purified by vacuum distillation.During the distillation practically the entire quantity of the substance is carriedover within a temperature interval of 1° to 2°C. The yield approaches thetheoretical amount. MP 68° to 69°C. BP 180° to 182°C at 4 mm Hg; 159° to160°C at 2 mm Hg. (Procedure is from US Patent 2,441,498.) |
| Brand name | Alphacaine (Carlisle); Lidoderm (Teikoku); Xylocaine(AstraZeneca）. |
| Therapeutic Function | Local anesthetic, Antiarrhythmic |
| General Description | Lidocaine was the first amino amide synthesized in 1948and has become the most widely used local anesthetic. Thetertiary amine has a pKa of 7.8 and it is formulated as thehydrochloride salt with a pH between 5.0 and 5.5. When lidocaineis formulated premixed with epinephrine the pH ofthe solution is adjusted to between 2.0 and 2.5 to prevent the hydrolysis of the epinephrine. Lidocaine is also availablewith or without preservatives. Some formulations of lidocainecontain a methylparaben preservative that maycause allergic reactions in PABA-sensitive individuals. Thelow pKa and medium water solubility provide intermediateduration of topical anesthesia of mucous membranes.Lidocaine can also be used for infiltration, peripheral nerveand plexus blockade, and epidural anesthesia. |
| Biological Activity | Anasthetic and class Ib antiarrhythmic agent.? Blocks voltage-gated sodium channels in the inactivated state. |
| Contact allergens | Lidocaine is an anesthetic of the amide group, like articaineor bupivacaine. Immediate-type IgE-dependentreactions are rare, and delayed-type contact dermatitisis exceptional. Cross-reactivity between the differentamide anesthetics is not systematic. |
| Biochem/physiol Actions | Na+ channel blocker; class IB antiarrhythmic that is rapidly absorbed after parenteral administration. |
| Pharmacology | Lidocaine is the most widely used local anaesthetic. It has a rapid onset andshort duration of action. Lidocaine is rapidly and extensively metabolised inthe liver and is safe at recommended doses. Efficacy is enhanced markedlyand duration of action prolonged by addition of adrenaline. Lidocaine is lesstoxic than bupivacaine; a testament to this relative safety is that lidocaine isused intravenously as a class 1b antiarrhythmic and as an i.v. infusion to treatrefractory chronic pain. Lidocaine solutions for injection are available inconcentrations of 1% and 2%, with or without adrenaline. It is also availableas a spray (4% or 10%), cream (2% or 4%), ointment or medicated plaster(both 5%) for topical application. |
| Pharmacokinetics | Lidocaine is administered intravenously because extensive first-pass transformation by the liver prevents clinically effective plasma concentrations orally. The drug is dealkylated and eliminated almost entirely by the liver; therefore, dosage adjustments are necessary in the presence of hepatic disease or dysfunction. Lidocaine clearance exhibits the time dependency common to high-clearance agents. With a continuous infusion lasting more than 24 hours, there is a decrease in total lidocaine clearance and an increase in elimination half-life compared with a single dose. Lidocaine free plasma levels can vary in certain patients owing to binding with albumin and the acutephase reactant a1-acid glycoprotein. Levels of a1-acid glycoprotein are increased in patients after surgery or acute myocardial infarction, whereas levels of both a1-acid glycoprotein and serum albumin are decreased in chronic hepatic disease or heart failure and in those who are malnourished. This is an essential consideration because it is the unbound fraction that is pharmacologically active. |
| Clinical Use | The metabolism of lidocaine is typical of the amino amideanesthetics . The liver is responsiblefor most of the metabolism of lidocaine and any decreasein liver function will decrease metabolism. Lidocaineis primarily metabolized by de-ethylation of the tertiary nitrogento form monoethylglycinexylidide (MEGX). At lowlidocaine concentrations, CYP1A2 is the enzyme responsiblefor most MEGX formation. At high lidocaine concentrations,both CYP1A2 and CYP3A4 are responsible for the formationof MEGX. |
| Side effects | Central nervous system side effects such as drowsiness, slurred speech, paresthesias, agitation, and confusion predominate. These symptoms may progress to convulsions and respiratory arrest with higher plasma concentrations. A rare adverse effect is malignant hyperthermia. Cimetidine significantly reduces the systemic clearance of lidocaine as well as the volume of distribution at steady state and the degree of plasma protein binding. Beta blockers also reduce lidocaine clearance owing to a decrease in hepatic blood flow. For the same reason, clearance is reduced in congestive heart failure or low-output states. Amiodarone may also influence the pharmacokinetics of lidocaine. In patients receiving amiodarone, single doses of intravenous lidocaine do not influence the pharmacokinetics of either agent. When amiodarone treatment is started in patients who are already receiving lidocaine infusion, there is a decrease in lidocaine clearance, which can result in toxic lidocaine levels. |
| Safety Profile | Poison by ingestion, intravenous, intraperitoneal, and subcutaneous routes. Human systemic effects: blood pressure lowering, changes in heart rate, coma, convulsions, dlstorted perceptions, dyspnea, excitement, hallucinations, muscle contraction or spasticity, pulse rate, respiratory depression, toxic psychosis. An experimental teratogen. Other experimental reproductive effects. A local anesthetic. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx. |
| Synthesis | Lidocaine, 2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide (2.2.2), is synthesized from 2,6-dimethylaniline upon reaction with chloroacetic acid chloride, which gives |á-chloro-2,6-dimethylacetanilide (2.1.1), and its subsequent reaction with diethylamine [11]. Synthesis of Lidocaine |
| Veterinary Drugs and Treatments | Besides its use as a local and topical anesthetic agent, lidocaine isused to treat ventricular arrhythmias, principally ventricular tachycardiaand ventricular premature complexes in all species. Cats maybe more sensitive to the drug and some clinicians feel that it shouldnot be used in this species as an antiarrhythmic, but this remainscontroversial. In horses, lidocaine may be useful to prevent postoperativeileus and reperfusion injury. |
| Electrophysiologic Effects | Experimentally, lidocaine has been found to prevent VF arising during myocardial ischemia or infarction by preventing the fragmentation of organized largewavefronts into heterogeneous wavelets. Although lidocaine is of proven benefit in preventing VF early after clinical myocardial infarction, there is no evidence that it reduces mortality. To the contrary, lidocaine may increase mortality after myocardial infarction by approximately 40% to 60%.There are no controlled studies of lidocaine in secondary prevention of recurrence of VT or VF. Lidocaine terminates organized monomorphic spontaneous VT or induced sustained VT in only approximately 20% of cases and is less effective than many other antiarrhythmic drugs. In a blinded, randomized study of intravenous lidocaine versus intravenous amiodarone in out-of-hospital VF resistant to defibrillation, lidocaine was associated with half the likelihood of survival to hospital admission compared with amiodarone. |
| Drug interactions | The concurrent administration of lidocaine with cimetidinebut not ranitidine may cause an increase (15%) inthe plasma concentration of lidocaine. This effect is amanifestation of cimetidine reducing the clearance andvolume of distribution of lidocaine. The myocardial depressanteffect of lidocaine is enhanced by phenytoinadministration. |
| Metabolism | Lidocaine is extensively metabolized in the liver by N-dealkylation and aromatic hydroxylationscatalyzed by CYP1A2 isozymes. Lidocaine also possesses a weak inhibitory activitytoward the CYP1A2 isozymes and, therefore, may interfere with metabolism of other medications. |
| storage | Store at RT |
| Toxicity evaluation | The potency of lidocaine depends on various factors includingage of the subject, weight, physique including obesity, vascularityof the site, and indication for use, as this would determinethe absorption and excretion rate. Physiologically,lidocaine blocks neuronal transmission by interfering with theflow of sodium across excitable membranes. A single lidocainemolecule binds to a single voltage-gated sodium channelimpeding the movement of sodium ions across neuronalmembranes. Consequently repolarization is prevented andfurther depolarization is not possible. Toxicity is dose relatedand results from excessive quantities of lidocaine. |
| Precautions | Contraindications include hypersensitivity to localanesthetics of the amide type (a very rare occurrence),severe hepatic dysfunction, a history of grand malseizures due to lidocaine, and age 70 or older. Lidocaineis contraindicated in the presence of second- or thirddegreeheart block, since it may increase the degree ofblock and can abolish the idioventricular pacemaker responsiblefor maintaining the cardiac rhythm. |
Lidocaine Preparation Products And Raw materials
| Raw materials | Diethylamine-->Chloroacetyl chloride-->N-Methylaniline-->Lidocaine hydrochloride-->[(2,6-DIMETHYLPHENYL)AMINOCARBONYLMETHYL]CHLORIDE-->2,6-Dimethylaniline-->2,6-DI-O-METHYL-BETA-CYCLODEXTRIN |
| Preparation Products | N-ETHYLLIDOCAINE BROMIDE-->3-Bromo Lidocaine |
