Amifampridine 20mg tablets
Prescription only
Requires a prescription from a doctor or prescriber
Tablet
20mg
Oral
Amifampridine, or 3,4-diaminopyridine (3,4-DAP), is a quaternary ammonium compound that blocks presynaptic potassium channels, and subsequently prolongs the action potential and increases presynaptic calcium concentrations [A33863].
Active ingredients:
Amifampridine
1 safety notice
Safety information for pregnancy and breastfeeding
Pregnancy
At doses higher than the recommended daily dose for humans, amifampridine caused a dose-related increase in the percentage of pregnant rats with stillborn offspring F272.
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
Report a side effect
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Official medicine documents
Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
Yellow Card reports
MHRA
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
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Suspected adverse reactions reported for Amifampridine
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Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
EMA
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
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Suspected adverse reactions reported for Amifampridine
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Learn about EU pharmacovigilance and safety monitoring
EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
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WHO defined daily dose (DDD)
40 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
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Clinical guidelines and formulary information
British National Formulary
Amifampridine
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
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Supply & product information
Official product databases and supply status monitoring
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Codes for healthcare professionals and prescribing systems
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These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
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SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
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Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
3.6 to 4.2 hours
Mechanism
Amifampridine is a symptomatic treatment that increases acetylcholine concentrations at the neuromuscular junction.
Food interactions
1 warning
Human targets
1 target
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
0.6 to 1.3 hours
Orally-administered amifampridine is rapidly absorbed in humans to reach the peak plasma concentrations within by 0.6…
Half-life
3.6 to 4.2 hours
The average elimination half-life of amifampridine was 3.6 to 4.2 hours and 4.1 to 4.8 hours for the 3-N-acetyl amifampridine metabolite.
[L36425]
[L36425]
Protein binding
25.3%
In vitro human plasma protein binding of amifampridine and 3-N-acetyl amifampridine was 25.3% and 43.3%, respectively.
[L36425]
[L36425]
Volume of distribution
2 mg/k
In healthy volunteers, the volume of distribution for plasma amifampridine indicated that RUZURGI is a drug with a moderate to a high volume of distribution.
[L36425]…
[L36425]…
Metabolism
Amifampridine is extensively metabolized by N-acetyltransferase 2 (NAT2) to 3-N-acetyl-amifampridine, which is considered an
inactive metabolite.
[L43312]…
inactive metabolite.
[L43312]…
Elimination
93%
Following oral administration, more than 93% of total amifampridine is renally eliminated within 24 hours .
[A33865]…
[A33865]…
Clearance
30 mg
Overall clearance of amifampridine is both metabolic and renal; it is primarily cleared from the plasma via metabolism by N-acetylation F272.…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Small molecule
About this compound
Amifampridine, or 3,4-diaminopyridine (3,4-DAP), is a quaternary ammonium compound that blocks presynaptic potassium channels, and subsequently prolongs the action potential and increases presynaptic calcium concentrations [A33863]. It was first discovered in Scotland in the 1970s and its clinical effectiveness for neuromuscular disorders, including Lambert–Eaton myasthenic syndrome (LEMS), has been investigated in the 1980s [L3171]. Amifampridine phosphate is a more stable salt that serves as an active ingredient of EMA-approved Firdapse, which was previously marketed as Zenas. It is currently used as the first-line symptomatic treatment for LEMS in adult patients and is ideally given as oral tablets in divided doses, three or four times a day. Firdapse (amifampridine) was formally approved by the US FDA for the treatment of adults with LEMS as recently as November of 2018 [L4819].
LEMS is a rare auto-immune disorder of the neuromuscular junction that is characterized by proximal muscle weakness, depressed tendon reflexes, and posttetanic potentiation in addition to autonomic dysfunction [A33863]. About 50-60% of the patients develop more rapidly progressive LEMS and small cell lung cancer, which influences the prognosis [A33863]. Patients with LEMS develop serum antibodies against presynaptic P/Q-type voltage-gated calcium channels, leading to decreased presynaptic calcium levels and reduced quantal release of acetylcholine, which is mainly responsible for causing symptoms of LEMS [A33863]. Reduced acetylcholine release at the neuromuscular junction leads to decreased frequency of miniature endplate potentials of normal amplitude, and insufficient acetylcholine levels for the activation of postsynaptic muscle fibers following a single nerve impulse [A33863]. This leads to the reduction of the compound muscle action potential (CMAP) [A33863]. Treatment for LEMS include immunotherapy such as conventional immunosuppression or intravenous immunoglobulins, however such treatments are recommended in patients in whom symptomatic treatment would not suffice [A33863]. Amifampridine is the nonimmune treatment options for LEMS.
In phase III clinical trials of adult patients with LEMS, treatment of amifampridine significantly improved symptoms of LEMS compared to placebo with good tolerance [A33864]. It was demonstrated in clinical studies involving healthy volunteers that the pharmacokinetics and systemic exposure to amifampridine is affected by the genetic differences in N-acetyl-transferase (NAT) enzymes (acetylator phenotype) and NAT2 genotype, which is subject to genetic variation F272. Slow acetylators were at higher risk for experiencing drug-associated adverse reactions, such as paresthesias, nausea, and headache F272.
LEMS is a rare auto-immune disorder of the neuromuscular junction that is characterized by proximal muscle weakness, depressed tendon reflexes, and posttetanic potentiation in addition to autonomic dysfunction [A33863]. About 50-60% of the patients develop more rapidly progressive LEMS and small cell lung cancer, which influences the prognosis [A33863]. Patients with LEMS develop serum antibodies against presynaptic P/Q-type voltage-gated calcium channels, leading to decreased presynaptic calcium levels and reduced quantal release of acetylcholine, which is mainly responsible for causing symptoms of LEMS [A33863]. Reduced acetylcholine release at the neuromuscular junction leads to decreased frequency of miniature endplate potentials of normal amplitude, and insufficient acetylcholine levels for the activation of postsynaptic muscle fibers following a single nerve impulse [A33863]. This leads to the reduction of the compound muscle action potential (CMAP) [A33863]. Treatment for LEMS include immunotherapy such as conventional immunosuppression or intravenous immunoglobulins, however such treatments are recommended in patients in whom symptomatic treatment would not suffice [A33863]. Amifampridine is the nonimmune treatment options for LEMS.
In phase III clinical trials of adult patients with LEMS, treatment of amifampridine significantly improved symptoms of LEMS compared to placebo with good tolerance [A33864]. It was demonstrated in clinical studies involving healthy volunteers that the pharmacokinetics and systemic exposure to amifampridine is affected by the genetic differences in N-acetyl-transferase (NAT) enzymes (acetylator phenotype) and NAT2 genotype, which is subject to genetic variation F272. Slow acetylators were at higher risk for experiencing drug-associated adverse reactions, such as paresthesias, nausea, and headache F272.
Properties:
View FDA drug labelsolid
Avg. mass: 109.13 Da
DrugBank indication
Amifampridine is indicated for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults and pediatric patients.
[L43312]
Nevertheless, at the current time only the Firdapse brand of amifampridine is indicated for the treatment of LEMS in both adult and pediatric patients, while the Ruzurgi brand of amifampridine is indicated for the treatment of LEMS only in patients aged 6 to less than 17 years.
[L43312][L36425]
[L43312]
Nevertheless, at the current time only the Firdapse brand of amifampridine is indicated for the treatment of LEMS in both adult and pediatric patients, while the Ruzurgi brand of amifampridine is indicated for the treatment of LEMS only in patients aged 6 to less than 17 years.
[L43312][L36425]
Also known as(28)
3,4 diaminopyridine
3,4-DAP
3,4-Diaminopyridine
3,4-Pyridinediamine
4,5-Diaminopyridine
Amifampridine
DAP
Voltage-gated K(+) channel HuKI
Dosage forms(3)
Tablet (Oral)
Tablet (Oral) — 10 mg/1
Tablet (Oral) — 10 mg
Molecular properties(18)
Drug interactions(516)
Known interactions with other medications. Always consult a healthcare professional.
Ivabradine
Moderate
Ivabradine may increase the QTc-prolonging activities of Amifampridine.
Dofetilide
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Dofetilide.
Citalopram
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Citalopram.
Anagrelide
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Anagrelide.
Disopyramide
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Disopyramide.
Clemastine
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Clemastine.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Ibutilide.
Valproic acid
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Valproic acid.
Terfenadine
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Terfenadine.
Grepafloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Grepafloxacin.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Sotalol.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Erlotinib.
Toremifene
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Toremifene.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Cisapride.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Imatinib.
Astemizole
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Astemizole.
Thioridazine
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Thioridazine.
Trovafloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Trovafloxacin.
Mifepristone
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Mifepristone.
Arsenic trioxide
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Arsenic trioxide.
Escitalopram
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Escitalopram.
Domperidone
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Domperidone.
Sparfloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Sparfloxacin.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Bepridil.
Paliperidone
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Paliperidone.
Lithium cation
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Lithium cation.
Temafloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Temafloxacin.
Zuclopenthixol
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Zuclopenthixol.
Tetrabenazine
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Tetrabenazine.
Dronedarone
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Dronedarone.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Nilotinib.
Iloperidone
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Iloperidone.
Vandetanib
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Vandetanib.
Romidepsin
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Romidepsin.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Asenapine.
Artemether
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Artemether.
Lumefantrine
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Lumefantrine.
Vemurafenib
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Vemurafenib.
Eliglustat
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Eliglustat.
Ribociclib
Unknown severity
The risk or severity of QTc prolongation can be increased when Ribociclib is combined with Amifampridine.
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Glasdegib.
Deutetrabenazine
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Deutetrabenazine.
Macimorelin
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Macimorelin.
Terodiline
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Terodiline.
Amiodarone
Unknown severity
The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Amiodarone.
Leuprolide
Unknown severity
The risk or severity of QTc prolongation can be increased when Leuprolide is combined with Amifampridine.
The risk or severity of QTc prolongation can be increased when Goserelin is combined with Amifampridine.
Erythromycin
Unknown severity
The risk or severity of QTc prolongation can be increased when Erythromycin is combined with Amifampridine.
Azithromycin
Unknown severity
The risk or severity of QTc prolongation can be increased when Azithromycin is combined with Amifampridine.
Moxifloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Moxifloxacin is combined with Amifampridine.
Showing 50 of 516 interactions
Food & lifestyle interactions
Advice
Take with or without food.
Toxicity & overdose
The approximate oral LD50 was >25mg/kg in rats and 100 mg/kg in mice.
[L50231]
The approximate intravenous LD50 was 25 mg/kg in both rats and mice.
[L50231]
Peritoneal and subcutaneous LD50 in mice were 20 mg/kg and 35 mg/kg, respectively.
[A33863]
There is limited clinical experienced with amifampridine overdose. The manifestations of acute drug overdose may include abdominal pain, and should be responded with discontinuation of treatment and initiation of supportive care with close monitoring of viral signs. There is no specific antidote known for amifampridine F272.
In vitro, amifampridine showed no clinically relevant carcinogenic or genotoxic potential.
However, in a 2-year rat study, amifampridine caused small but statistically significant dose-related increases in the incidence of Schwannomas in both genders and of endometrial carcinomas in females F272. At doses higher than the recommended daily dose for humans, amifampridine caused a dose-related increase in the percentage of pregnant rats with stillborn offspring F272. Effects on the central and autonomic nervous system, increased liver and kidney weights and cardiac effects (second degree atrioventricular block) were seen in a repeat-dose toxicity studies in rats and dogs F272.
[L50231]
The approximate intravenous LD50 was 25 mg/kg in both rats and mice.
[L50231]
Peritoneal and subcutaneous LD50 in mice were 20 mg/kg and 35 mg/kg, respectively.
[A33863]
There is limited clinical experienced with amifampridine overdose. The manifestations of acute drug overdose may include abdominal pain, and should be responded with discontinuation of treatment and initiation of supportive care with close monitoring of viral signs. There is no specific antidote known for amifampridine F272.
In vitro, amifampridine showed no clinically relevant carcinogenic or genotoxic potential.
However, in a 2-year rat study, amifampridine caused small but statistically significant dose-related increases in the incidence of Schwannomas in both genders and of endometrial carcinomas in females F272. At doses higher than the recommended daily dose for humans, amifampridine caused a dose-related increase in the percentage of pregnant rats with stillborn offspring F272. Effects on the central and autonomic nervous system, increased liver and kidney weights and cardiac effects (second degree atrioventricular block) were seen in a repeat-dose toxicity studies in rats and dogs F272.
How it works
Mechanism of action
Amifampridine is a symptomatic treatment that increases acetylcholine concentrations at the neuromuscular junction. It selectively blocks presynaptic fast voltage-gated potassium channels, thereby prolonging cell membrane depolarization and action potential, and augmenting calcium transport into the nerve endings. Increased intracellular calcium enhances the exocytosis of acetylcholine-containing vesicles and enhances impulse transmission at central, autonomic, and neuromuscular synapses [A33863, F272]. Amifampridine improves muscle strength and resting compound muscle action potential (CMAP) amplitudes with an overall weighted mean difference of 1.69 mV F272.
Pharmacodynamics
Administration of amifampridine to patients with LES in clinical trials resulted in improvement of the compound muscle action potential (CMAP), muscle function, and quantitative myasthenia gravis (QMG) score [A33863]. One case of a slight prolongation of the QTc interval in male patient with LEMS and euthyroid Hashimoto’s disease treated with 90 mg of amifampridine in combination with 100 mg azathioprine was reported [A33863]. In vitro, amifampridine was shown to modulate cardiac conduction and induce phasic contractions in different arteries from several species [A33863]. In addition, it stimulated potassium-evoked dopamine and noradrenaline release in rat hippocampal slices and upregulate acetylcholine release in the brain [A33863]. It may also potentiate adrenergic and cholinergic neuromuscular transmission in the gatrointestinal tract [A33863]. In a single pharmacokinetic study, no effect was observed of amifampridine phosphate on cardiac repolarization as assessed using the QTc interval F272. There were no changes in heart rate, atrioventricular conduction or cardiac depolarization as measured by the heart rate, PR and QRS interval durations F272.
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Orally-administered amifampridine is rapidly absorbed in humans to reach the peak plasma concentrations within by 0.6 to 1.3 hours F272. A single oral dose of 20 mg amifampridine in fasted individuals resulted in mean peak plasma concentrations (Cmax) ranging from 16 to 137 ng/mL F272. Bioavailability is approximately 93-100% based on recoveries of unmetabolised amifampridine and a major 3-N-acetylated amifampridine metabolite in urine F272.
Food consumption decreases amifampridine absorption and exposure with a decrease in the time to reach maximum concentrations (Tmax) .
[A33865]
It is approximated that food consumption lowers the Cmax on average by ~44% and lowers AUC by ~20%. based on geometric mean ratios F272.
Systemic exposure to amifampridine is affected by the overall metabolic acetylation activity of NAT enzymes and NAT2 genotype .
[A33881]
The NAT enzymes are highly polymorphic that results in variable slow acetylator (SA) and rapid acetylator (RA) phenotypes. Slow acetylators are more prone to increased systemic exposure to amifampridine, and may require higher doses for therapeutic efficacy [A33881, F272].
Food consumption decreases amifampridine absorption and exposure with a decrease in the time to reach maximum concentrations (Tmax) .
[A33865]
It is approximated that food consumption lowers the Cmax on average by ~44% and lowers AUC by ~20%. based on geometric mean ratios F272.
Systemic exposure to amifampridine is affected by the overall metabolic acetylation activity of NAT enzymes and NAT2 genotype .
[A33881]
The NAT enzymes are highly polymorphic that results in variable slow acetylator (SA) and rapid acetylator (RA) phenotypes. Slow acetylators are more prone to increased systemic exposure to amifampridine, and may require higher doses for therapeutic efficacy [A33881, F272].
Half-life
The average elimination half-life of amifampridine was 3.6 to 4.2 hours and 4.1 to 4.8 hours for the 3-N-acetyl amifampridine metabolite.
[L36425]
[L36425]
Protein binding
In vitro human plasma protein binding of amifampridine and 3-N-acetyl amifampridine was 25.3% and 43.3%, respectively.
[L36425]
[L36425]
Volume of distribution
In healthy volunteers, the volume of distribution for plasma amifampridine indicated that RUZURGI is a drug with a moderate to a high volume of distribution.
[L36425]
After a 2 mg/kg infusion in rats, the volume of distribution at steady-state was 2.8 ± 0.7 L/kg.
[A252822]
Drug concentrations were highest in organs of excretion, including the liver, kidney, and the gastrointestinal tract, and some tissues of glandular function, such as lacrimal, salivary, mucous, pituitary, and thyroid glands F272. Concentrations in tissues are generally similar to or greater than concentrations in plasma F272.
[L36425]
After a 2 mg/kg infusion in rats, the volume of distribution at steady-state was 2.8 ± 0.7 L/kg.
[A252822]
Drug concentrations were highest in organs of excretion, including the liver, kidney, and the gastrointestinal tract, and some tissues of glandular function, such as lacrimal, salivary, mucous, pituitary, and thyroid glands F272. Concentrations in tissues are generally similar to or greater than concentrations in plasma F272.
Metabolism
Amifampridine is extensively metabolized by N-acetyltransferase 2 (NAT2) to 3-N-acetyl-amifampridine, which is considered an
inactive metabolite.
[L43312]
inactive metabolite.
[L43312]
Route of elimination
Following oral administration, more than 93% of total amifampridine is renally eliminated within 24 hours .
[A33865]
About 19% of the total renally-excreted dose is in the parent drug form, and about 74-81.7% of the dose is in its metabolite form F272.
[A33865]
About 19% of the total renally-excreted dose is in the parent drug form, and about 74-81.7% of the dose is in its metabolite form F272.
Clearance
Overall clearance of amifampridine is both metabolic and renal; it is primarily cleared from the plasma via metabolism by N-acetylation F272. Following oral administration of a single 20 or 30 mg dose of RUZURGI to healthy volunteers, amifampridine apparent oral clearance (CL/F) was 149 to 214 L/h.
[L36425]
[L36425]
Drug targets(1)
Proteins and enzymes this drug interacts with in the body
Potassium voltage-gated channel subfamily A member 1
KCNA1
blocker
Specific functiondelayed rectifier potassium channel activity
Cellular location
Cell membrane
General function & pharmacology
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney .
PMID:19903818 PMID:8845167
Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability .
PMID:17156368
Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane .
PMID:19912772
Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel .
PMID:12077175 PMID:17156368
Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels .
PMID:12077175 PMID:17156368
In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure .
PMID:19307729 PMID:19903818 PMID:19912772 PMID:19968958
In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation .
PMID:17156368
Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability.
Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity).
Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses .
PMID:11026449 PMID:17136396
Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity).
The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential PMID:19307729 PMID:23903368
PMID:19903818 PMID:8845167
Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability .
PMID:17156368
Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane .
PMID:19912772
Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel .
PMID:12077175 PMID:17156368
Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels .
PMID:12077175 PMID:17156368
In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure .
PMID:19307729 PMID:19903818 PMID:19912772 PMID:19968958
In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation .
PMID:17156368
Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability.
Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity).
Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses .
PMID:11026449 PMID:17136396
Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity).
The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential PMID:19307729 PMID:23903368
Metabolizing enzymes(2)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
NAT1Arylamine N-acetyltransferase 1
substrate
NAT2Arylamine N-acetyltransferase 2
substrate
Transporters(1)
Proteins that transport this drug across cell membranes
Solute carrier family 22 member 2
SLC22A2
inhibitor
Specific functionacetylcholine transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics .
PMID:9260930 PMID:9687576
Functions as a Na(+)-independent, bidirectional uniporter .
PMID:21128598 PMID:9687576
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient .
PMID:15212162 PMID:9260930 PMID:9687576
However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow .
PMID:15783073
Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters .
PMID:16581093 PMID:17460754 PMID:9687576
Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system .
PMID:17460754
Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium .
PMID:15817714
Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) .
PMID:12089365 PMID:15212162 PMID:17072098 PMID:24961373 PMID:9260930
Mediates the uptake and efflux of quaternary ammonium compound choline .
PMID:9260930
Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine .
PMID:12538837 PMID:21128598
Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) .
PMID:11907186
Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) .
PMID:12395288 PMID:16394027
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
PMID:9260930 PMID:9687576
Functions as a Na(+)-independent, bidirectional uniporter .
PMID:21128598 PMID:9687576
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient .
PMID:15212162 PMID:9260930 PMID:9687576
However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow .
PMID:15783073
Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters .
PMID:16581093 PMID:17460754 PMID:9687576
Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system .
PMID:17460754
Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium .
PMID:15817714
Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) .
PMID:12089365 PMID:15212162 PMID:17072098 PMID:24961373 PMID:9260930
Mediates the uptake and efflux of quaternary ammonium compound choline .
PMID:9260930
Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine .
PMID:12538837 PMID:21128598
Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) .
PMID:11907186
Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) .
PMID:12395288 PMID:16394027
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Scientific references(5)
Lindquist S., Stangel M.
Update on treatment options for Lambert-Eaton myasthenic syndrome: focus on use of amifampridine.
Neuropsychiatr Diseases Treat
20117:341-9. doi: 10.2147/NDT.S10464. Epub 2011 May 30
Oh S.J., Shcherbakova N., Kostera-Pruszczyk A., Alsharabati M., Dimachkie M., Blanco J.M., Brannagan T., Lavrnic D., Shieh P.B., Vial C., Meisel A., Komoly S., Schoser B., Sivakumar K., So Y.
Amifampridine phosphate (Firdapse((R))) is effective and safe in a phase 3 clinical trial in LEMS.
Muscle Nerve
2016 May53(5):717-25. doi: 10.1002/mus.25070. Epub 2016 Mar 3
Haroldsen P.E., Musson D.G., Hanson B., Quartel A., O'Neill C.A.
Effects of Food Intake on the Relative Bioavailability of Amifampridine Phosphate Salt in Healthy Adults.
Clinical Therapeutics
2015 Jul 137(7):1555-63. doi: 10.1016/j.clinthera.2015.05.498. Epub 2015 Jun 20
Haroldsen P.E., Sisic Z., Datt J., Musson D.G., Ingenito G.
Acetylator Status Impacts Amifampridine Phosphate (Firdapse) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.
Clinical Therapeutics
2017 Jul39(7):1360-1370. doi: 10.1016/j.clinthera.2017.05.353. Epub 2017 Jun 19
Ishida N., Kondo Y., Chikano Y., Kobayashi-Nakade E., Suga Y., Ishizaki J., Komai K., Matsushita R.
Pharmacokinetics and tissue distribution of 3,4-diaminopyridine in rats.
Biopharm Drug Disposition
2019 Sep40(8):294-301. doi: 10.1002/bdd.2203
ATC classification(1 code)
ATC N07XX05
International brands(2)
Salt forms(1)
Amifampridine phosphate(DBSALT002818)
Experimental properties(2)
Protein Data Bank entries(1)
Commercial products(8)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Amifampridine
Additional database identifiers
Drugs Product Database (DPD)
23495
ChemSpider
5705
BindingDB
50416493
PDB
L89
ZINC
ZINC000000164000
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6218
GenAtlas
KCNA1
GeneCards
KCNA1
GenBank Gene Database
L02750
GenBank Protein Database
186663
Guide to Pharmacology
538
UniProt Accession
KCNA1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7645
GeneCards
NAT1
GenBank Gene Database
D90041
GenBank Protein Database
219414
UniProt Accession
ARY1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7646
GeneCards
NAT2
GenBank Gene Database
D90040
GenBank Protein Database
219412
UniProt Accession
ARY2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10966
GeneCards
SLC22A2
GenBank Gene Database
X98333
GenBank Protein Database
2281942
Guide to Pharmacology
1020
UniProt Accession
S22A2_HUMAN
Patent information
6 active patents
10626088
United States
Approved 21 Apr 2020 · Expires 25 Feb 2037
10y 11m
10793893
United States
Approved 6 Oct 2020 · Expires 7 Apr 2034
8 years
11060128
United States
Approved 13 Jul 2021 · Expires 29 Jun 2032
6y 2m
11274332
United States
Approved 15 Mar 2022 · Expires 29 Jun 2032
6y 2m
11274331
United States
Approved 15 Mar 2022 · Expires 29 Jun 2032
6y 2m
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated about 1 month ago(4 Mar 2026)