| Candidate ID: | R0103 |
| Source ID: | DB00281 |
| Source Type: | approved; vet_approved |
| Compound Type: |
small molecule
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| Compound Name: |
Lidocaine
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| Synonyms: |
2-(Diethylamino)-2',6'-acetoxylidide; 2-(Diethylamino)-N-(2,6-dimethylphenyl)acetamide; alpha-diethylamino-2,6-dimethylacetanilide; Lidocaine; Lignocaine; α-diethylamino-2,6-dimethylacetanilide
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| Molecular Formula: |
C14H22N2O
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| SMILES: |
CCN(CC)CC(=O)NC1=C(C)C=CC=C1C
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| Structure: |
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| DrugBank Description: |
Ever since its discovery and availability for sale and use in the late 1940s, lidocaine has become an exceptionally commonly used medication . In particular, lidocaine's principal mode of action in acting as a local anesthetic that numbs the sensations of tissues means the agent is indicated for facilitating local anesthesia for a large variety of surgical procedures . It ultimately elicits its numbing activity by blocking sodium channels so that the neurons of local tissues that have the medication applied on are transiently incapable of signaling the brain regarding sensations . In doing so, however, it can block or decrease muscle contractile, resulting in effects like vasodilation, hypotension, and irregular heart rate, among others . As a result, lidocaine is also considered a class Ib anti-arrhythmic agent . Nevertheless, lidocaine's local anesthetic action sees its use in many medical situations or circumstances that may benefit from its action, including the treatment of premature ejaculation .
Regardless, lidocaine is currently available as a relatively non-expensive generic medication that is written for in millions of prescriptions internationally on a yearly basis. It is even included in the World Health Organization's List of Essential Medicines .
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| CAS Number: |
137-58-6
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| Molecular Weight: |
234.3373
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| DrugBank 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 .
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| DrugBank Pharmacology: |
Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure . 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 . The net effect is normally a modest hypotension when the recommended dosages are not exceeded .
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 . 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 .
Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base . 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 . This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection . 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 .
Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation . 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 .
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| DrugBank MoA: |
Lidocaine is a local anesthetic of the amide type . It is used to provide local anesthesia by nerve blockade at various sites in the body . 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 . In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes . At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions . 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 . 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 . 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 .
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 . 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 .
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| Targets: |
Sodium channel protein type 10 subunit alpha inhibitor; Sodium channel protein type 9 subunit alpha inhibitor; Sodium channel protein type 5 subunit alpha inhibitor; Epidermal growth factor receptor antagonist; Sodium channel protein type 4 subunit alpha; Alpha-1-acid glycoprotein 1; Alpha-1-acid glycoprotein 2
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| Inclusion Criteria: |
Therapeutic strategy associated
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