Bupivacaine
[CAS# 2180-92-9]

Identification

• Classification: API >> Anesthetic agents >> Local anesthetics
• Name: Bupivacaine
• Synonyms: 1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
• Molecular Formula: C₁₈H₂₈N₂O
• Molecular Weight: 288.43
• Protein Sequence: X
• CAS Registry Number: 2180-92-9
• EC Number: 218-553-3
• SMILES: CCCCN1CCCCC1C(=O)NC2=C(C=CC=C2C)C

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Boiling point: 423.4±45.0 °C 760 mmHg (Calc.)^*
• Flash point: 209.9±28.7 °C (Calc.)^*
• Index of refraction: 1.547 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06 Danger
• Risk Statements: H300-H310-H330
• Safety Statements: P260-P262-P264-P270-P271-P280-P284-P301+P316-P302+P352-P304+P340-P316-P320-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	2	H330
Acute toxicity	Acute Tox.	1	H310
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	2	H300

• Transport Information: UN 2811

Discovery and Applications

Bupivacaine is a widely used amide-type local anesthetic known for its long duration of action and potent anesthetic effects. It functions by blocking voltage-gated sodium channels in nerve cell membranes, which prevents the initiation and propagation of nerve impulses, leading to a reversible loss of sensation in the area where it is administered. Bupivacaine is commonly employed for regional anesthesia techniques, including epidural, spinal, peripheral nerve blocks, and infiltration anesthesia.

Bupivacaine was first synthesized in the 1950s and introduced into clinical practice shortly thereafter as an improvement over earlier local anesthetics. Its development aimed to provide prolonged anesthesia with good potency and manageable toxicity. Bupivacaine’s chemical structure is characterized by a butyl group attached to the nitrogen of the amide linkage, which contributes to its lipophilicity and duration of action.

The hydrochloride salt of bupivacaine is the form most commonly used in medical settings. It is available in various concentrations and formulations, including solutions for injection, often combined with vasoconstrictors such as epinephrine to prolong anesthetic effects and reduce systemic absorption. The drug exhibits a relatively slow onset compared to agents like lidocaine but provides anesthesia lasting from two to eight hours depending on the dose, concentration, and site of administration.

Clinically, bupivacaine is preferred in procedures that require extended anesthesia, such as major surgeries, labor epidurals, and postoperative pain management. Its potency and prolonged effect make it particularly useful for continuous infusion in epidural analgesia. However, it is known for a higher risk of cardiotoxicity compared to other local anesthetics, especially when inadvertently injected intravascularly or in high doses, necessitating careful dosing and monitoring.

Pharmacokinetically, bupivacaine is absorbed from the injection site at a rate dependent on the vascularity of the tissue. It is extensively bound to plasma proteins, primarily alpha-1 acid glycoprotein, which affects its distribution and duration. Bupivacaine is metabolized hepatically via cytochrome P450 enzymes to inactive metabolites that are excreted mainly in urine. The elimination half-life ranges between 2.7 to 3.5 hours.

Adverse effects associated with bupivacaine include central nervous system symptoms such as dizziness, tinnitus, or seizures in cases of systemic toxicity. Cardiovascular effects can be severe, including arrhythmias and cardiac depression, which have led to the development of lipid emulsion therapy as an effective treatment for bupivacaine-induced cardiotoxicity.

Bupivacaine’s clinical use requires appropriate technique to avoid complications, including aspiration before injection to prevent intravascular administration and dose adjustment in patients with hepatic impairment or other risk factors. Its efficacy and duration have made it a cornerstone in regional anesthesia practice.

In summary, bupivacaine is a long-acting amide local anesthetic widely used for regional anesthesia and analgesia. Its potent anesthetic effect, combined with prolonged duration, supports its use in major surgical and obstetric procedures, while its known toxicity profile necessitates careful clinical management.

References

1979. Melanin Capacity to Accumulate Drugs in the Internal Ear: A Study on Lidocaine, Bupivacaine and Chlorpromazine. Acta Oto-Laryngologica, 88(1-2).
DOI: 10.3109/00016487909137141

1991. Electrophysiologic effects of bupivacaine in the isolated rabbit heart. Anesthesia and Analgesia, 72(1).
DOI: 1984378

2000. Bupivacaine Release from Biopolymeric Depots for the Alleviation of Postoperative Pain. Biomaterials Engineering and Devices: Human Applications.
DOI: 10.1007/978-1-59259-196-1_19