Mexiletine

Mexiletine
Clinical data
Trade names	Mexitil, NaMuscla
AHFS/Drugs.com	Monograph
MedlinePlus	a607064
License data	US DailyMed: Mexiletine;
Pregnancy; category	AU: B1; ;
Routes of; administration	By mouth, intravenous
ATC code	C01BB02 (WHO) ;
Legal status
Legal status	CA: ℞-only; UK: POM (Prescription only); US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	90%
Protein binding	50–60%
Metabolism	Liver (CYP2D6 and 1A2-mediated)
Elimination half-life	10–12 hours
Excretion	Kidney (10%)
Identifiers
	IUPAC name (RS)-1-(2,6-dimethylphenoxy)propan-2-amine; OR2-(2-aminopropoxy)-1,3-dimethylbenzene;
CAS Number	31828-71-4 ;
PubChem CID	4178;
IUPHAR/BPS	2629;
DrugBank	DB00379 ;
ChemSpider	4034 ;
UNII	1U511HHV4Z;
KEGG	D08215 ; as HCl: D00639 ;
ChEBI	CHEBI:6916 ;
ChEMBL	ChEMBL558 ;
CompTox Dashboard (EPA)	DTXSID8048446 ;
ECHA InfoCard	100.046.190
Chemical and physical data
Formula	C11H17NO
Molar mass	179.263 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES O(c1c(cccc1C)C)CC(N)C;
	InChI InChI=1S/C11H17NO/c1-8-5-4-6-9(2)11(8)13-7-10(3)12/h4-6,10H,7,12H2,1-3H3 ; Key:VLPIATFUUWWMKC-UHFFFAOYSA-N ;
	(verify)

Mexiletine (INN) (sold under the brand names Mexitil and Namuscla) is a medication used to treat abnormal heart rhythms, chronic pain, and some causes of muscle stiffness. Common side effects include abdominal pain, chest discomfort, drowsiness, headache, and nausea. It works as a non-selective voltage-gated sodium channel blocker and belongs to the Class IB group of anti-arrhythmic medications.^[2]

Medical uses

Mexiletine has several uses including the treatment of abnormal heart rhythms or arrhythmias, chronic pain, and myotonia.

In general when treating arrhythmias, mexiletine is reserved for use in dangerous heart rhythm disturbances such as ventricular tachycardia.^[3] It is of particular use when treating arrhythmias caused by long QT syndrome.^[4] The LQT3 form of long QT syndrome is amenable to treatment with mexiletine as this form is caused by defective sodium channels that continue to release a sustained current rather than fully inactivating, however other forms of long QT syndrome can also be treated with this medication.^[4]

Mexiletine has been used to treat chronic pain and may also be used to treat muscle stiffness resulting from myotonic dystrophy (Steinert's disease) or nondystrophic myotonias such as myotonia congenita (Thomsen syndrome or Becker syndrome).^[5]^[6]

Adverse effects

Common side effects of mexiletine include abdominal pain, chest discomfort, drowsiness, headache, nausea and skin reactions.^[7] Uncommon or rare side effects include seizures and liver dysfunction.^[7]

Pharmacology

Mexiletine is an oral analogue of lidocaine.^[6] It is a class IB antiarrhythmic which shorten the refractory period and action potential duration (APD). Decrease in APD more than that of ERP so there is increase ERP/APD ratio.^[3] The drug has a bioavailability of 90%, and peak plasma concentrations are seen after 2–4 hours.^[3] The mean drug half-life is approximately 11 hours.^[3] Mexiletine is predominantly metabolised by the liver. The pharmacokinetics of mexiletine are preserved with even moderate to severe renal impairment, but dose adjustment may be required when creatinine clearance falls below 10 mL/minute.^[3]

Synthesis

Mexiletine synthesis:^[8]

Society and culture

Mexiletine is available for human use in the US, and has been reintroduced in the UK as a licensed product, having previously only been available as a 'named patient' import. The drug is sold under the trade name Mexitil for use in arrhythmias and NaMuscla for use in myotonia.^[9]^[10]

Veterinary uses

Mexiletine is available to veterinarians in the US for the treatment of heart disease in dogs.^{[medical citation needed]} It is commonly used for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxer dogs in combination with sotalol.^{[medical citation needed]}

References

^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
^ Canavero S, Bonicalzi V (13 October 2011). Central Pain Syndrome: Pathophysiology, Diagnosis and Management. Cambridge University Press. pp. 286–. ISBN 978-1-107-01021-5.
^ ^a ^b ^c ^d ^e Manolis AS, Deering TF, Cameron J, Estes NA (May 1990). "Mexiletine: pharmacology and therapeutic use". Clinical Cardiology. 13 (5): 349–59. doi:10.1002/clc.4960130509. PMID 2189614. S2CID 269453.
^ ^a ^b Li G, Zhang L (November 2018). "The role of mexiletine in the management of long QT syndrome". Journal of Electrocardiology. 51 (6): 1061–1065. doi:10.1016/j.jelectrocard.2018.08.035. PMID 30497731. S2CID 54167081.
^ Romman A, Salama-Hanna J, Dwivedi S (September 2018). "Mexiletine Usage in a Chronic Pain Clinic: Indications, Tolerability, and Side Effects". Pain Physician. 21 (5): E573–E579. doi:10.36076/ppj.2018.5.E573 (inactive 1 November 2024). PMID 30282405. S2CID 52917253.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
^ ^a ^b Sweetman S, ed. (2002). Martindale: The complete drug reference (33rd ed.). London: Pharmaceutical Press. ISBN 0-85369-499-0.
^ ^a ^b "Mexiletine". British National Formulary. NICE. Retrieved 2019-06-17.
^ US 3954872, Koppe R, Kummer W, "1-(2{40 ,6{40 -Dimethyl-phenoxy)-2-amino-alkanes and salts thereof", issued 1976, assigned to Boehringer Sohn Ingelheim.
^ "Mexiletine". www.drugbank.ca. Retrieved 2019-06-17.
^ "Lupin announces launch of NaMuscla". www.biospectrumindia.com. Retrieved 2019-06-17.