General
Preferred name
LIDOCAINE
Synonyms
LIDOCAINE HYDROCHLORIDE ()
Lignocaine ()
Alphacaine ()
Lignocaine hydrochloride ()
Lidocaine HCL ()
Lidothesin ()
Xyloneural ()
Xylocaine ()
Lidocaďne hydrochloride ()
Lidocaine (Alphacaine) ()
Lidocaine (hydrochloride) ()
Lidocaine HCL, Lidothesin, Lignocaine hydrochloride, Xyloneural ()
Lidocaine-d10 ()
Lignocaine HCl ()
LMX 4 ()
Xylestesin ()
Vagisil ()
NSC-40030 ()
Lidoderm ()
ALGRX-3268 ()
Dentipatch ()
Anestacon ()
Octocaine ()
Oraqix ()
Xylotox ()
Embolex ()
Iontocaine ()
Ztlido ()
Solarcaine ()
ALGRX 3268 ()
Xylodase ()
Lignostab ()
Lidopen ()
Lidocainum ()
Lidocaton ()
Xylotox E80 ()
Glydo ()
NSC-757420 ()
Lidocaine hydrochloride preservative free ()
Lidocaine Viscous ()
Instillagel ()
Alphacaine hydrochloride ()
Laryngojet ()
Lignospan Special ()
Xylocaine preservative free ()
Lidocaine hydrochloride usp ()
Lidocaine hydrochloride anhydrous ()
Lido HCL ()
Akten ()
Lignostab N ()
Xylocaine hydrochloride ()
Emla ()
Dequaspray ()
Iglu ()
Hemocane ()
Laryngotracheal Anesthesia Kit ()
Anhydrous lidocaine hydrochloride ()
Lignostab A 100 ()
Xylocaine Dental ()
Calgel ()
Pediatric Lta Kit ()
Versatis ()
Lidocaini hydrochloridum ()
Anodesyn ()
Bradosol Plus ()
Zingo ()
Lignostab-A ()
Lignocaine (as hydrochloride) ()
Lidocaine Hydrochloride Viscous ()
LTA II Kit ()
Co-Phenylcaine Fte ()
Germoloids ()
Germoloids Complete ()
Medijel ()
Preparation H ()
Xylocaine Viscous ()
Rexocaine ()
Lignokent ()
Oragard ()
Lidocaine hydrochloride monohydrate ()
Laryng-O-Jet Kit ()
Denela ()
Bismodyne ()
P&D ID
PD003120
CAS
6108-05-0
73-78-9
137-58-6
851528-09-1
Tags
available
natural product
drug
Approved by
FDA
First approval
1948
Drug indication
Anesthetic (local)
Anaesthesia
Anesthetic (local),Anesthetic (topical)
Dysmenorrhea
Drug Status
vet_approved
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION
Lidocaine is an anesthetic of the amide group indicated for production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks [F4349, L5930].
ROE
The excretion of unchanged lidocaine and its metabolites occurs predominantly via the kidney with less than 5% in the unchanged form appearing in the urine [F4349, L5930]. The renal clearance is inversely related to its protein binding affinity and the pH of the urine [L5930]. This suggests by the latter that excretion of lidocaine occurs by non-ionic diffusion [L5930].
METABOLISM
Lidocaine is metabolized predominantly and rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys [F4349, L5930]. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation [F4349, L5930]. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide [F4349, L5930]. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine HCl [F4349, L5930]. Approximately 90% of lidocaine HCl administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged [F4349, L5930]. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline [F4349, L5930].
ABSORPTION
In general, lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin [F4468]. The agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream [F4468]. And although lidocaine is also well absorbed across the gastrointestinal tract the oral bioavailability is only about 35% as a result of a high degree of first-pass metabolism [F4468]. After injection into tissues, lidocaine is also rapidly absorbed and the absorption rate is affected by both vascularity and the presence of tissue and fat capable of binding lidocaine in the particular tissues [F4468].; ; The concentration of lidocaine in the blood is subsequently affected by a variety of aspects, including its rate of absorption from the site of injection, the rate of tissue distribution, and the rate of metabolism and excretion [F4349, L5930, L5948]. Subsequently, the systemic absorption of lidocaine is determined by the site of injection, the dosage given, and its pharmacological profile [F4349, L5930, L5948]. The maximum blood concentration occurs following intercostal nerve blockade followed in order of decreasing concentration, the lumbar epidural space, brachial plexus site, and subcutaneous tissue [F4349, L5930, L5948]. The total dose injected regardless of the site is the primary determinant of the absorption rate and blood levels achieved [F4349, L5930, L5948]. There is a linear relationship between the amount of lidocaine injected and the resultant peak anesthetic blood levels [F4349, L5930, L5948].; ; Nevertheless, it has been observed that lidocaine hydrochloride is completely absorbed following parenteral administration, its rate of absorption depending also on lipid solubility and the presence or absence of a vasoconstrictor agent [F4349, L5930, L5948]. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration [F4349, L5930, L5948].; ; Additionally, lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion [F4349].
HALF-LIFE
The elimination half-life of lidocaine hydrochloride following an intravenous bolus injection is typically 1.5 to 2.0 hours [F4349]. Because of the rapid rate at which lidocaine hydrochloride is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics [F4349]. The half-life may be prolonged two-fold or more in patients with liver dysfunction [F4349].
DESCRIPTION
Lidocaine was the first-in-class amino amide-type local anesthetic to be discovered.
(GtoPdb)
PHARMACODYNAMICS
Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure [F4349, L5930]. With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present [F4349, L5930]. The net effect is normally a modest hypotension when the recommended dosages are not exceeded [F4349, L5930].; ; In particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction [F4349, L5930, L5948]. Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse [F4349, L5930, L5948].; ; Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base [L5948]. As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values [L5948]. This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection [L5930]. The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection [L5930].; ; Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation [L5948]. This effect could be due to acidosis decreasing the amount of un-ionized lidocaine molecules, a more rapid reduction in lidocaine concentration as a result of increased blood flow, or potentially also because of increased production of inflammatory mediators like peroxynitrite that elicit direct actions on sodium channels [L5948].
MOA
Lidocaine is a local anesthetic of the amide type [F4349, L5930, L5948]. It is used to provide local anesthesia by nerve blockade at various sites in the body [F4349, L5930, L5948]. It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action [F4349, L5930, L5948]. In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes [F4349, L5930, L5948]. At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions [F4349, L5930, L5948]. The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization [F4349, L5930, L5948]. As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential [F4349, L5930, L5948]. This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place [F4349, L5930, L5948].; ; In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system [F4349, L5930, L5948]. After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction [F4349, L5930, L5948].
DESCRIPTION
Anti-arrhythmic; local anesthetic
(LOPAC library)
DESCRIPTION
KV11.1 (hERG) channel activator; antiarrhythmic
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
27
AdooQ Bioactive Compound Library
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
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Enamine BioReference Compounds
Guide to Pharmacology
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
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ReFrame library
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[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
101
Molecular Weight
234.17
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
1
Rotatable Bonds
5
Ring Count
1
Aromatic Ring Count
1
cLogP
2.58
TPSA
32.34
Fraction CSP3
0.5
Chiral centers
0.0
Largest ring
6.0
QED
0.85
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
NF-¦ÊB
H1 receptor
Sodium Channel
EGFR, SCN10A, SCN5A, SCN9A
ERK
MEK
Histamine Receptor
EGFR
Pathway
GPCR/G protein
Immunology/Inflammation
Neuroscience
Membrane Transporter/Ion Channel
Apoptosis
MAPK/ERK Pathway
NF-κB
Stem Cell/Wnt
Primary Target
Voltage-gated Sodium (NaV) Channels
MOA
Blocker
Histamine Receptor agonist
Indication
itching, eczema, hemorrhage
Disease Area
neurology/psychiatry, dermatology, hematology
Therapeutic Class
Anesthetics
VGSC Target
Nav1.3
Nav1.4
Nav1.5
Nav1.7
Nav1.9
Source data
