Bupivacaine Property

Melting point:

107.5-108°

Boiling point:

430.65°C (rough estimate)

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)

InChI

InChI=1S/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)

InChIKey

LEBVLXFERQHONN-UHFFFAOYSA-N

SMILES

C1(CCCCN1CCCC)C(=O)NC1C(C)=CC=CC=1C

CAS DataBase Reference

2180-92-9(CAS DataBase Reference)

NIST Chemistry Reference

2-Piperidinecarboxamide, 1-butyl-n-(2,6-dimethylphenyl)-(2180-92-9)

EPA Substance Registry System

2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)- (2180-92-9)

Safety

Hazard Codes 

T+

Risk Statements 

26/27/28-38-41

Safety Statements 

22-26-36/37/39-45

RIDADR 

2811

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H300Fatal if swallowed

H310Fatal in contact with skin

H315Causes skin irritation

H318Causes serious eye damage

H330Fatal if inhaled

Precautionary statements

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P262Do not get in eyes, on skin, or on clothing.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P284Wear respiratory protection.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P302+P350IF ON SKIN: Gently wash with plenty of soap and water.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P310Immediately call a POISON CENTER or doctor/physician.

P320Specific treatment is urgent (see … on this label).

P321Specific treatment (see … on this label).

P322Specific measures (see …on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P361Remove/Take off immediately all contaminated clothing.

P362Take off contaminated clothing and wash before reuse.

P363Wash contaminated clothing before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

Bupivacaine Chemical Properties,Usage,Production

Originator

Carbostesin,Astra,W. Germany,1967

Uses

Anesthetic (local).

Uses

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.

Definition

ChEBI: 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide is a piperidinecarboxamide obtained by formal condensation of the carboxy group of N-butylpipecolic acid with the amino group of 2,6-dimethylaniline. It is a piperidinecarboxamide, an aromatic amide and a tertiary amino compound. It is a conjugate base of a 1-butyl-2-[(2,6-dimethylphenyl)carbamoyl]piperidinium.

brand name

Marcaine (Hospira); Sensorcaine (AstraZeneca).

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].