2180-92-9

Basic information

• Product Name: Bupivacaine
• Synonyms: MARCAINE;BUPIVACAINE;BUPIVACAINE BASE;(.+/-.)-1-Butyl-2',6'-pipecoloxylidide;1-Butyl-2-(2,6-xylycarbamoyl)piperidine;1-Butyl-2',6'-pipecoloxylidide;1-butyl-2’,6’-pipecoloxylidide;1-butyl-n-(2,6-dimethylphenyl)-2-piperidinecarboxamid
• CAS NO: 2180-92-9
• Molecular Formula: C₁₈H₂₈N₂O
• Molecular Weight: 288.43
• EINECS: 218-553-3
• Product Categories: Active Pharmaceutical Ingredients;research chemical
• Mol File: 2180-92-9.mol
• Article Data: 9

Chemical Properties

• Melting Point: 107.5-108°
• Boiling Point: 430.65°C (rough estimate)
• Flash Point: 140.9oC
• Appearance: /
• Density: 1.0238 (rough estimate)
• Refractive Index: 1.5700 (estimate)
• PKA: 8.09; also reported as 8.17(at 25℃)
• Water Solubility: 101.5mg/L(25 oC)
• CAS DataBase Reference: Bupivacaine(CAS DataBase Reference)
• NIST Chemistry Reference: Bupivacaine(2180-92-9)
• EPA Substance Registry System: Bupivacaine(2180-92-9)

Safety Data

• Hazard Codes: T+
• Statements: 26/27/28-38-41
• Safety Statements: 22-26-36/37/39-45
• RIDADR: 2811
• Hazardous Substances Data: 2180-92-9(Hazardous Substances Data)

Usage

Chemical Description

Bupivacaine is a local anesthetic that is often used in epidural anesthesia.

Uses

Different sources of media describe the Uses of 2180-92-9 differently. You can refer to the following data:
1. Anesthetic (local).
2. Like lidocaine and mepivacaine, bupivacaine is used in infiltration, spinal, and epidural anesthesia in blocking nerve transmission. Its most distinctive property is its long-lasting action. It is used for surgical intervention in urology and in lower thoracic surgery from 3 to 5 h in length, and in abdominal surgery lasting from 45 to 60 min. It is used to block the trifacial nerve, the sacral and brachial plexuses, in resetting dislocations, in epidural anesthesia, and during Cesarian sections.

Therapeutic Function

Local anesthetic

General Description

Bupivacaine was synthesized simultaneously with mepivacainein 1957 but was at first overlooked because of the increasedtoxicity compared with mepivacaine. When themethyl on the cyclic amine of mepivacaine is exchanged fora butyl group the lipophilicity, potency and the duration ofaction all increase. Literature reports of cardiovascular toxicity,including severe hypotension and bradycardia, areabundant in the literature.91 Bupivacaine is highly bound toplasma proteins (95%), and thus the free concentration mayremain low until all of the protein binding sites are occupied.After that point, the plasma levels of bupivacaine rise rapidlyand patients may progress to overt cardiac toxicity withoutever showing signs of CNS toxicity. The cardiotoxicity ofbupivacaine is a result of its affinity to cardiac tissues and itsability to depress electrical conduction and predispose theheart to reentry types of arrhythmias. The cardiotoxicity ofbupivacaine was found to be significantly more prominentwith the “R” isomer, or the racemic mixture, thus the “S”stereoisomer is now on the market as levobupivacaine.

Mechanism of action

Bupivacaine is a local anaesthetic containing a chiral centre and adopts dextro and laevo forms. The enantiopure l form is less cardio- and neurotoxic and has an equivalent potency to the racemic mixture; therefore levobupivacaine is often preferred to reduce the potential for toxicity. Stereoselectivity describes the differences in response at a given receptor for the different enantiomers (such as the response discussed for S(+) ketamine). The opioid and NMDA receptors also exhibit stereoselectivity.

Pharmacology

Bupivacaine is a chiral compound used clinically for 50 years, with a slower onset, greater potency and longer duration of action than lidocaine. Initial benefits of bupivacaine were sensory–motor separation and minimal tachyphylaxis, unlike repeated doses of lidocaine. However, it has greater potential for cardiac toxicity, related to its avid binding to and slow dissociation from cardiac N a+ channels. Inadvertent intravenous administration may result in systemic toxicity (see later), and it is contraindicated for intravenous regional anaesthesia.Bupivacaine is commonly used for epidural administration in obstetrics and postoperative pain management. A hyperbaric preparation containing 80 mg ml-1 glucose is available for spinal anaesthesia.

Side effects

Common side effects of bupivacaine include:weakness, long-lasting numbness or tingling;feeling restless or drowsy;tremors;headache, blurred vision;fast or slow heartbeats;breathing problems;chills or shivering;back pain; nausea, vomiting.

Synthesis

Bupivacaine, N-2,6-(dimethyl)1-butyl-2-piperidincarboxamide (2.2.7), is chemically similar to mepivacaine and only differs in the replacement of the N-methyl substituent on the piperidine ring with an N-butyl substituent. There are also two suggested methods of synthesis. The first comes from α-picolin-2,6-xylidide (2.2.4). The alkylation of the last with butyl bromide gives the corresponding pyridine salt (2.2.6). Finally, it is reduced by hydrogen using platinum oxide as a catalyst into a piperidine derivative—bupivacaine. The other method results directly from the piperidine-2-carboxylic acid chloride, which is reacted with 2,6-dimethylaniline. The resulting amide (2.2.8) is further alkylated with butyl bromide to bupivacaine [17–19].

InChI:InChI=1/C18H28N2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21)

Upstream product

• 109-65-9 1-bromo-butane 
• 856838-98-7 racemic 1-butylpiperidine-2-carboxylic acid 
• 87-62-7 2,6-dimethylaniline 
• 98-98-6 2-Picolinic acid 
• 39627-98-0 2-pyridine-carboxamide-N-(2,6-dimethylphenyl) 
• 123-72-8 butyraldehyde 
• 4043-87-2 pipecolic Acid 
• 27262-45-9 (+)-Bupivacaine 
• 14252-80-3 bupivacaine hydrochloride 

Downstream Products

• 27262-45-9 (+)-Bupivacaine 
• 27262-47-1 levobupivacaine 

Relevant articles and documents

HYDROPHOBIC ACID ADDITION SALTS AND PHARMACEUTICAL FORMULATIONS THEREOF

The invention provides hydrohphobic drug salts and pharmaceutical compositions comprising such salts. The invention fourther provides compositions for delivering poorly soluble drugs, including hydrophobic drug salts.

Preparation method of levobupivacaine hydrochloride

The invention belongs to the technical field of chemical synthesis and in particular relates to a preparation method of levobupivacaine hydrochloride. The preparation method takes racemic or S-configuration 2-piperidinecarboxylic acid as a starting raw material and comprises the following steps: taking the starting raw material and n-butylaldehyde to react and carrying out borohydride reduction reaction to obtain 1-butylpiperidine-2-carboxylic acid; taking the 1-butylpiperidine-2-carboxylic acid and 2,6-dimethylaniline to be subjected to condensation reaction, so as to generate bupivacaine or levobupivacaine; carrying out subsequent treatment to obtain a final product levobupivacaine hydrochloride. Compared with an existing synthesis route, the preparation method has the advantages of short synthesis route, simple method, convenience for operation, low cost and easiness for industrial production; reaction conditions of each step are relatively moderate, a process is stable, a strong-corrosion chlorination reagent is not used, the pollution to environment is reduced and the like.

DERMAL COMPOSITIONS OF SUBSTITUTED AMIDES AND THE USE THEREOF AS MEDICATION FOR PAIN AND PRURITUS

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