The only other treatment approved for LEMS (Firdapse) is only approved for use in adults. Medical uses
Amifampridine is used to treat many of the congenital myasthenic syndromes, particularly those with defects in choline acetyltransferase, downstream kinase 7, and those where any kind of defect causes "fast channel" behaviour of the acetylcholine receptor. It is also used to treat symptoms of Lambert–Eaton myasthenic syndrome. Contraindications
Because it affects voltage-gated ion channels in the heart, it is contraindicated in people with long QT syndrome and in people taking a drug that might prolong QT time like sultopride, disopyramide, cisapride, domperidone, rifampicin or ketoconazol. It is also contraindicated in people with epilepsy or badly controlled asthma. Adverse effects
The dose-limiting side effects include tingling or numbness, difficulty sleeping, fatigue, and loss of muscle strength.Amifampridine can cause seizures, especially but not exclusively when given at high doses and/or in particularly vulnerable individuals who have a history of seizures. Interactions
The combination of amifampridine with pharmaceuticals that prolong QT time increases the risk of ventricular tachycardia, especially torsade de pointes; and combination with drugs that lower the seizure threshold increases the risk of seizures. Interactions via the livers cytochrome P450 enzyme system are considered unlikely. Pharmacology
Mechanism of action
In Lambert–Eaton myasthenic syndrome, acetylcholine release is inhibited as antibodies involved in the host response against certain cancers cross-react with Ca2+ channels on the prejunctional membrane. Amifampridine works by blocking potassium channel efflux in nerve terminals so that action potential duration is increased.
A possible association with deletion of the gene GPC1, which encodes a glypican 1-a heparan sulfate proteoglycan, has been reported. This gene is located on the long arm of chromosome 2 (2q37) and is involved in the regulation of inflammation and the Hedgehog gene.Egyptian infants with biliary atresia were found to have null GSTM1 genotype while all their mothers were heterozygous for GSTM1. Thus these infants may be protected in utero by their maternal detoxification system, yet once born they cannot handle the detoxification of an aflatoxin load. Toxins
Some cases of biliary atresia may result from exposure to aflatoxin B1, and to a lesser extent aflatoxin B2 during late pregnancy. Intact maternal detoxification protects baby during intrauterine life, yet after delivery, the baby struggles with the aflatoxin in its blood and liver. Moreover, the baby feeds aflatoxin M1 from its mom, as aflatoxin M1 is the detoxification product of aflatoxin B1. It is a milder toxin that causes cholangitis in the baby.There are isolated examples of biliary atresia in animals. For instance, lambs born to sheep grazing on land contaminated with a weed (Red Crumbweed) developed biliary atresia at certain times. The plants were later found to contain a toxin, now called biliatresone Studies are ongoing to determine whether there is a link between human cases of biliary atresia and toxins such as biliatresone. There are some indications that a metabolite of certain human gut bacteria may be similar to biliatresone.