U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C14H22N2O.CH2O3
Molecular Weight 296.3621
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LIDOCAINE BICARBONATE

SMILES

OC(O)=O.CCN(CC)CC(=O)NC1=C(C)C=CC=C1C

InChI

InChIKey=QOKQKHSBEYXQLP-UHFFFAOYSA-N
InChI=1S/C14H22N2O.CH2O3/c1-5-16(6-2)10-13(17)15-14-11(3)8-7-9-12(14)4;2-1(3)4/h7-9H,5-6,10H2,1-4H3,(H,15,17);(H2,2,3,4)

HIDE SMILES / InChI

Molecular Formula CH2O3
Molecular Weight 62.0248
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C14H22N2O
Molecular Weight 234.3373
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Lidocaine is a local anesthetic and cardiac depressant used to numb tissue in a specific area and for management of cardiac arrhythmias, particularly those of ventricular origins, such as occur with acute myocardial infarction. Lidocaine alters signal conduction in neurons by blocking the fast voltage-gated Na+ channels in the neuronal cell membrane responsible for signal propagation. With sufficient blockage, the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anesthetic effect by not merely preventing pain signals from propagating to the brain, but by stopping them before they begin. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations also affect other modalities of neuron signaling. Lidocaine exerts an antiarrhythmic effect by increasing the electrical stimulation threshold of the ventricle during diastole. In usual therapeutic doses, lidocaine hydrochloride produces no change in myocardial contractility, in systemic arterial pressure, or an absolute refractory period. The efficacy profile of lidocaine as a local anesthetic is characterized by a rapid onset of action and intermediate duration of efficacy. Therefore, lidocaine is suitable for infiltration, block, and surface anesthesia. Longer-acting substances such as bupivacaine are sometimes given preference for spinal and epidural anesthesias; lidocaine, though, has the advantage of a rapid onset of action. Lidocaine is also the most important class-1b antiarrhythmic drug; it is used intravenously for the treatment of ventricular arrhythmias (for acute myocardial infarction, digoxin poisoning, cardioversion, or cardiac catheterization) if amiodarone is not available or contraindicated. Lidocaine should be given for this indication after defibrillation, CPR, and vasopressors have been initiated. A routine preventative dose is no longer recommended after a myocardial infarction as the overall benefit is not convincing. Inhaled lidocaine can be used as a cough suppressor acting peripherally to reduce the cough reflex. This application can be implemented as a safety and comfort measure for patients who have to be intubated, as it reduces the incidence of coughing and any tracheal damage it might cause when emerging from anesthesia. Adverse drug reactions (ADRs) are rare when lidocaine is used as a local anesthetic and is administered correctly. Most ADRs associated with lidocaine for anesthesia relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, and allergic reactions only rarely occur. Systemic exposure to excessive quantities of lidocaine mainly result in a central nervous system (CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations.

Originator

Sources: Arkiv foer Kemi, Mineralogi och Geologi (1946), A22, (No. 18), 30 pp.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
XYLOCAINE

Approved Use

INDICATIONS & USAGE Lidocaine Hydrochloride Oral Topical Solution USP, 2% (Viscous) is indicated for the production of topical anesthesia of irritated or inflamed mucous membranes of the mouth and pharynx. It is also useful for reducing gagging during the taking of X-ray pictures and dental impressions.

Launch Date

1951
Primary
VIAFLEX

Approved Use

Indications and Usage Lidocaine hydrochloride administered intravenously is specifically indicated in the acute management of (1) ventricular arrhythmias occurring during cardiac manipulations, such as cardiac surgery and (2) life-threatening arrhythmias which are ventricular in origin, such as occur during acute myocardial infarction.

Launch Date

1984
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
212 ng/mL
84 mg 1 times / day steady-state, topical
dose: 84 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
LIDOCAINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
231 ng/mL
84 mg 2 times / day steady-state, topical
dose: 84 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
LIDOCAINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4100 ng × h/mL
84 mg 1 times / day steady-state, topical
dose: 84 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
LIDOCAINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4704 ng × h/mL
84 mg 2 times / day steady-state, topical
dose: 84 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
LIDOCAINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.81 h
84 mg 1 times / day steady-state, topical
dose: 84 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
LIDOCAINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.94 h
84 mg 2 times / day steady-state, topical
dose: 84 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
LIDOCAINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Other AEs: Nausea and vomiting, Hallucinations...
Other AEs:
Nausea and vomiting (1%)
Hallucinations (8 patients)
Tachycardia (4 patients)
Tremor (3 patients)
Hypotension (2 patients)
Light-headed (1 patient)
Phlebitis (1 patient)
Hypertension (1 patient)
Sources:
800 mg single, intravenous
Overdose
Dose: 800 mg
Route: intravenous
Route: single
Dose: 800 mg
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Condition: hypertensive, severe precordial pain
Age Group: 57 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 1.6%)
Sources:
700 mg 1 times / day steady, transdermal
Recommended
Dose: 700 mg, 1 times / day
Route: transdermal
Route: steady
Dose: 700 mg, 1 times / day
Sources:
unhealthy, adult
n = 404
Health Status: unhealthy
Condition: Neuropathic pain
Age Group: adult
Sex: unknown
Population Size: 404
Sources:
5 % 1 times / day steady, transdermal
Dose: 5 %, 1 times / day
Route: transdermal
Route: steady
Dose: 5 %, 1 times / day
Sources:
unhealthy, adult
n = 300
Health Status: unhealthy
Condition: post-herpetic neuralgia and diabetic polyneuropathy
Age Group: adult
Sex: M+F
Population Size: 300
Sources:
Disc. AE: Headache, Application site irritation...
AEs leading to
discontinuation/dose reduction:
Headache (2 patients)
Application site irritation (2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypertension 1 patient
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Light-headed 1 patient
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Phlebitis 1 patient
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Nausea and vomiting 1%
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Hypotension 2 patients
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Tremor 3 patients
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Tachycardia 4 patients
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Hallucinations 8 patients
2 mg 1 times / day steady, intravenous
Dose: 2 mg, 1 times / day
Route: intravenous
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 17 - 66 years
n = 68
Health Status: unhealthy
Condition: chronic daily headache and chronic cluster headache
Age Group: 17 - 66 years
Sex: M+F
Population Size: 68
Sources:
Death grade 5, 1.6%
Disc. AE
800 mg single, intravenous
Overdose
Dose: 800 mg
Route: intravenous
Route: single
Dose: 800 mg
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Condition: hypertensive, severe precordial pain
Age Group: 57 years
Sex: M
Population Size: 1
Sources:
Application site irritation 2 patients
Disc. AE
5 % 1 times / day steady, transdermal
Dose: 5 %, 1 times / day
Route: transdermal
Route: steady
Dose: 5 %, 1 times / day
Sources:
unhealthy, adult
n = 300
Health Status: unhealthy
Condition: post-herpetic neuralgia and diabetic polyneuropathy
Age Group: adult
Sex: M+F
Population Size: 300
Sources:
Headache 2 patients
Disc. AE
5 % 1 times / day steady, transdermal
Dose: 5 %, 1 times / day
Route: transdermal
Route: steady
Dose: 5 %, 1 times / day
Sources:
unhealthy, adult
n = 300
Health Status: unhealthy
Condition: post-herpetic neuralgia and diabetic polyneuropathy
Age Group: adult
Sex: M+F
Population Size: 300
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
yes (co-administration study)
Comment: CYP1A2 is the enzyme principally responsible for the metabolic disposition of lidocaine in subjects with normal liver function.
Page: -
yes
yes (co-administration study)
Comment: Itraconazole and erythromycin had virtually no effect on the pharmacokinetics of intravenous lidocaine, but erythromycin slightly prolonged the elimination half-life (t½) of lidocaine (Study I). When lidocaine was taken orally, both erythromycin and itraconazole increased the peak concentration (Cmax) and the area under the concentration-time curve (AUC) of lidocaine by 40-70% (Study II).
Page: -
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Bretylium Tosylate; adverse effects in acute myocardial infarction.
1975 Apr
Etidocaine, bupivacaine, and lidocaine seizure thresholds in monkeys.
1975 Apr
Infiltrated lidocaine 2% with epinephrine 1:80,000 causes more postoperative pain than lidocaine 2% after oral soft tissue surgery.
1999 Spring
Vestibular schwannoma surgery and headache.
2000
Induction pain perception after premedication with propofol vs lidocaine: a pilot study.
2000 Apr
Lidocaine-induced conduction disturbance in patients with systemic hyperkalemia.
2000 Dec
Changes in seizure susceptibility to local anesthetics by repeated administration of cocaine and nomifensine but not GBR12935: possible involvement of noradrenergic system.
2000 Jul
A decrease in seizure susceptibility to lidocaine in kindled epileptic rats.
2000 May
Peripheral lidocaine but not ketamine inhibits capsaicin-induced hyperalgesia in humans.
2000 Oct
The incidence of transient neurological symptoms after spinal anaesthesia with lidocaine compared to prilocaine.
2000 Oct
The effect of systemic lidocaine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers.
2000 Oct
Potential neurotoxicity of spinal anesthesia with lidocaine.
2000 Sep
Pharmacological management of pain and anxiety during emergency procedures in children.
2001
Computerised advice on drug dosage to improve prescribing practice.
2001
[Comment on the article "Use of EMLA cream and ropivacaine indacryocystorhinostomy with locoregional anesthesia and sedation"].
2001 Apr
Comparison of topical and intravenous lignocaine with thiopentone for insertion of laryngeal mask airway.
2001 Apr
Giant R-waves in a patient with an acute inferior myocardial infarction.
2001 Apr
A dose-response study of adrenaline combined with lignocaine 2%: effect on acute postoperative pain after oral soft tissue surgery.
2001 Apr
Excision of a giant hydatid cyst of the lung under thoracic epidural anaesthesia.
2001 Apr
Effect of phloretin on the percutaneous absorption of lignocaine across human skin.
2001 Apr
A randomised, double-blind, placebo-controlled, comparative study of topical skin analgesics and the anxiety and discomfort associated with venous cannulation.
2001 Apr 28
Surgical treatment of anal fissures under local anesthesia.
2001 Feb
The efficacy of topical anaesthesia in flexible nasendoscopy: a double-blind randomised controlled trial.
2001 Feb
A randomized comparison of low-dose ketamine and lignocaine infiltration with ketamine-diazepam anaesthesia for post partum tubal ligation in Vanuatu.
2001 Feb
Oral sucrose compares favourably with lidocaine-prilocaine cream for pain relief during venepuncture in neonates.
2001 Feb
Topical anesthesia for phacoemulsification and painless subconjunctival antibiotic injection.
2001 Feb
Articaine hydrochloride: a study of the safety of a new amide local anesthetic.
2001 Feb
Lidocaine and prilocaine toxicity in a patient receiving treatment for mollusca contagiosa.
2001 Feb
Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat.
2001 Feb 1
The role of nitrergic system in lidocaine-induced convulsion in the mouse.
2001 Jan
The effect of an intrauterine application of two percent lignocaine gel on pain perception during Vabra endometrial sampling: a randomised double-blind, placebo-controlled trial.
2001 Jan
Influence of patient posture on oxygen saturation during fibre-optic bronchoscopy.
2001 Jan
Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs.
2001 Jan
Evaluation of caudal anaesthesia performed in conscious ex-premature infants for inguinal herniotomies.
2001 Jan
Hyperpigmentation following the use of Emla cream.
2001 Jan
Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance.
2001 Jan 1
Degeneracy and additional alloreactivity of drug-specific human alpha beta(+) T cell clones.
2001 Jul
Effects of local anesthetics on the contractility of rat bladders.
2001 Jun
Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea-pig cornea.
2001 Jun 1
Arrhythmogenic right ventricular dysplasia/cardiomyopathy in a Siberian husky.
2001 Mar
Reducing postnatal pain from perineal tears by using lignocaine gel: a double-blind randomized trial.
2001 Mar
LET versus EMLA for pretreating lacerations: a randomized trial.
2001 Mar
EMLA anaesthetic cream for sharp leg ulcer debridement: a review of the clinical evidence for analgesic efficacy and tolerability.
2001 Mar-Apr
Patient-administered nitrous oxide/oxygen inhalation provides safe and effective analgesia for percutaneous liver biopsy: a randomized placebo-controlled trial.
2001 May
The use of pre-cannulation local anaesthetic and factors affecting pain perception in the emergency department setting.
2001 May
The anesthetic onset and duration of a new lidocaine/prilocaine gel intra-pocket anesthetic (Oraqix) for periodontal scaling/root planing.
2001 May
Plasma levels of lidocaine and prilocaine after application of Oraqix, a new intrapocket anesthetic, in patients with advanced periodontitis.
2001 May
Inclusion of lignocaine base into a polar lipid formulation--in vitro release, duration of peripheral nerve block and arterial blood concentrations in the rat.
2001 May
Safety and pharmacokinetics of EMLA in the treatment of postburn pruritus in pediatric patients: a pilot study.
2001 May-Jun
Evaluation of pain management interventions for neonatal circumcision pain.
2001 May-Jun
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/08816s032lbl.pdf
Therapy of ventricular arrhythmias is often initiated with a single IV bolus of 1.0 to 1.5 mg/kg at a rate of 25 to 50 mg/min. of lidocaine hydrochloride injection. Following acute treatment by bolus in patients in whom arrhythmias tend to recur and who are incapable of receiving oral antiarrhythmic agents, intravenous infusion of Lidocaine Hydrochloride and 5% Dextrose Injection, USP is administered continuously at the rate of 1 to 4 mg/min (0.020 to 0.050 mg/kg/min in the average 70 kg adult). The 0.4% solution (4 mg/mL) can be given at a rate of 15 to 60 mL/hr (0.25 to 1 mL/min). The 0.8% solution (8 mg/mL) can be given at a rate of 7.5 to 30 mL/hr (0.12 to 0.5 mL/min). Precise dosage regimen is determined by patient characteristics and response.
Route of Administration: Other
Cells were prepared by dissociation from T175 cell culture flasks using trypsineEDTA (0.05%), cells were kept in serum free media in the cell hotel on board the QPatch HT. These cells were sampled, washed and re-suspended in extracellular recording solution by the QPatch HT immediately before application to well site on the chip. Once in whole-cell configuration, vehicle (0.1% DMSO v/v) was applied to the cells to achieve a stable control recording (4-min total). This was followed by application of test concentrations as a single bolus addition (4-min incubation per test concentration). Lidocaine were prepared in extracellular recording solution from a 10mM(100% DMSO) stock to yield a final 10 mkM(0.1% DMSO) test concentration from which subsequent serial dilutions in extracellular solution were performed (0.3-10 mkM). Voltage protocols for the sodium channels being screened were designed to reflect the high-frequency, pathophysiological state of the channels that may be therapeutic targets (Nav1.3, Nav1.4 and Nav1.7), and the lowfrequency, physiological state of the safety target (Nav1.5). Currents were elicited from NaV1.3, NaV1.4 and NaV1.7 cell lines using a standard two-pulse voltage protocol. From a holding potential of -100 mV, a 20 ms activating step to -20 mV was applied to assess the effect of compounds on resting (closed) state block. The second activating pulse was applied following a 5-s pre-pulse to half inactivation potential (variable depending on the sodium channel studied, -65 to -75 mV) to assess block on the openinactivated state of the channel. This protocol was applied at a sweep interval of 0.067 Hz throughout the duration of the experiment.
Substance Class Chemical
Created
by admin
on Sat Dec 16 02:06:30 GMT 2023
Edited
by admin
on Sat Dec 16 02:06:30 GMT 2023
Record UNII
2DO9G6G1JY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LIDOCAINE BICARBONATE
Common Name English
ACETAMIDE, 2-(DIETHYLAMINO)-N-(2,6-DIMETHYLPHENYL)-, COMPD. WITH CARBONIC ACID (1:1)
Systematic Name English
LIDOCAINE HYDROGEN CARBONATE
Common Name English
Code System Code Type Description
CAS
856323-35-8
Created by admin on Sat Dec 16 02:06:30 GMT 2023 , Edited by admin on Sat Dec 16 02:06:30 GMT 2023
PRIMARY
PUBCHEM
25050300
Created by admin on Sat Dec 16 02:06:30 GMT 2023 , Edited by admin on Sat Dec 16 02:06:30 GMT 2023
PRIMARY
FDA UNII
2DO9G6G1JY
Created by admin on Sat Dec 16 02:06:30 GMT 2023 , Edited by admin on Sat Dec 16 02:06:30 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY