U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C5H7N3
Molecular Weight 109.1294
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMIFAMPRIDINE

SMILES

c1c[nH]cc(c1=N)N

InChI

InChIKey=OYTKINVCDFNREN-UHFFFAOYSA-N
InChI=1S/C5H7N3/c6-4-1-2-8-3-5(4)7/h1-3H,7H2,(H2,6,8)

HIDE SMILES / InChI
Amifampridine (Firdapse), currently approved in the European Union, is the first and only approved drug for the symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) in adults, a rare autoimmune disease with the primary symptoms of muscle weakness. In LEMS, the body’s own immune system attacks connections between nerves and muscles and disrupts the ability of nerve cells to send signals to muscle cells. Amifampridine blocks voltage-dependent potassium channels, thereby prolonging pre-synaptic cell membrane depolarization. Prolonging the action potential enhances the transport of calcium into the nerve ending. The resulting increase in intracellular calcium concentrations facilitates exocytosis of acetylcholine containing vesicles, which in turn enhances neuromuscular transmission. Amifampridine phosphate has been granted Orphan Drug Designation and Breakthrough Therapy designation by the FDA for the treatment of Lambert-Eaton Myasthenic Syndrome (LEMS).

CNS Activity

Curator's Comment:: Amifampridine (3,4-DAP) displays toxicity largely due to blood-brain-barrier (BBB) penetration.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Firdapse

Approved Use

Symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults.

Launch Date

1.26152645E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
59.1 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
40.6 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
189 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
3-N-ACETYL-AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
268 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
3-N-ACETYL-AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
117 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
109 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
1220 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
3-N-ACETYL-AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
1444 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
3-N-ACETYL-AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.5 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.28 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
4.03 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
3-N-ACETYL-AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
4.1 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
3-N-ACETYL-AMIFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
100 mg 1 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Other AEs: Paresthesia, Dysesthesia...
Other AEs:
Paresthesia (69%)
Dysesthesia (69%)
Oral dysesthesia (69%)
Abdominal pain (25%)
Upper abdominal pain (25%)
Dyspepsia (17%)
Dizziness (12%)
Nausea (10%)
Back pain (8%)
Hypoesthesia (6%)
Muscle spasms (6%)
Sources:
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Other AEs: Convulsion, Head titubation...
Other AEs:
Convulsion (0.6%)
Head titubation (0.6%)
Tremor (0.6%)
Unresponsive to stimuli (0.6%)
Small cell lung cancer (0.6%)
Metastases to central nervous system (0.6%)
Lung cancer metastatic (0.6%)
Pulmonary mass (0.6%)
Bradycardia (0.6%)
Pneumonia (0.6%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea 10%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Dizziness 12%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Dyspepsia 17%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Abdominal pain 25%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Upper abdominal pain 25%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Hypoesthesia 6%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Muscle spasms 6%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Dysesthesia 69%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Oral dysesthesia 69%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Paresthesia 69%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Back pain 8%
10 mg 3 times / day multiple, oral
Recommended
Dose: 10 mg, 3 times / day
Route: oral
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
healthy, adult
n = 52
Health Status: healthy
Age Group: adult
Population Size: 52
Sources:
Bradycardia 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Convulsion 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Head titubation 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Lung cancer metastatic 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Metastases to central nervous system 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Pneumonia 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Pulmonary mass 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Small cell lung cancer 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Tremor 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
Unresponsive to stimuli 0.6%
75 mg 1 times / day multiple, oral (typical)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, adult
n = 162
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 162
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [Inhibition 30 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [IC50 490.9 uM]
yes [IC50 524.8 uM]
yes
yes
yes
Drug as victimTox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Validation of a CE assay for the analysis of isomeric aminopyridines and diaminopyridines.
2001 Feb
Persistence of botulinum neurotoxin A demonstrated by sequential administration of serotypes A and E in rat EDL muscle.
2001 Feb-Mar
Theoretical analysis of the molecular determinants responsible for the K(+) channel blocking by aminopyridines.
2001 Jun 15
Aminopyridines for symptomatic treatment in multiple sclerosis.
2002
Improvement of dy/dy dystrophic diaphragm by 3,4-diaminopyridine.
2002 Jul
Treatment for Lambert-Eaton myasthenic syndrome.
2003
Wheel-running exercise alters rat diaphragm action potentials and their regulation by K+ channels.
2003 Aug
Electrophysiological and pharmacological characterization of K+-currents in muscle fibres isolated from the ventral sucker of Fasciola hepatica.
2004 Dec
Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine.
2004 Jun 8
NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation.
2005 Jun 16
Taicatoxin inhibits the calcium-dependent slow motility of mammalian outer hair cells.
2005 May
Fetal exposure to 3,4-diaminopyridine in a pregnant woman with congenital myasthenia syndrome.
2006 Apr
Inotropic effects of the K+ channel blocker 3,4-diaminopyridine: differential responses of rat soleus and extensor digitorum longus.
2006 Dec
[Fatigue and episodic exhaustion as a feature of multiple sclerosis].
2006 Mar
Childhood myasthenia: clinical subtypes and practical management.
2007 Aug
Beneficial effects of 3,4-diaminopyridine on positioning downbeat nystagmus in a circumscribed uvulo-nodular lesion.
2007 Aug
Myasthenia gravis and Lambert-Eaton myasthenic syndrome in the same patient.
2007 Jul
[Treatment of Lambert-Eaton syndrome with 3,4- diaminopyridine and pyridostigmine].
2007 Jul-Aug
Molecular docking study of the binding of aminopyridines within the K+ channel.
2007 May
Long-lasting in vivo inotropic effects of the K(+) channel blocker 3,4-diaminopyridine during fatigue-inducing stimulation.
2008 Dec
[Lambert-Eaton Myasthenic Syndrome associated with vocal cord carcinoma].
2008 Jan
Autoantibodies in neuromuscular transmission disorders.
2008 Jul
Onset dynamics of type A botulinum neurotoxin-induced paralysis.
2008 Jun
Therapeutic strategies in congenital myasthenic syndromes.
2008 Oct
[A case of Lambert-Eaton myasthenic syndrome with small cell lung cancer, treated with 3,4-diaminopyridine].
2009 Jan
3,4-Diaminopyridine is more effective than placebo in a randomized, double-blind, cross-over drug study in LEMS.
2009 Nov
3,4-diaminopyridine safety in clinical practice: an observational, retrospective cohort study.
2010 Jun
Patents

Sample Use Guides

Amifampridine (Firdapse) should be given in divided doses, three or four times a day. The recommended starting dose is 15 mg a day, which can be increased in 5 mg increments every 4 to 5 days, to a maximum of 60 mg per day. No single dose should exceed 20 mg. Tablets are to be taken with food. For oral use only.
Route of Administration: Oral
In Vitro Use Guide
In nerve terminal regions of axons in rat olfactory cortex in the presence of tetraethylammonium (TEA, 5 mM) and Cd2+ (100 uM), the K(+)-component was depressed by Amifampridine (3,4-DAP; 1 to 20 uM; IC50 2.0 +/- 0.4 uM).
Name Type Language
AMIFAMPRIDINE
DASH   EMA EPAR   INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
AMIFAMPRIDINE [MI]
Common Name English
3,4 DIAMINOPYRIDINE
VANDF  
Systematic Name English
AMIFAMPRIDINE [ORANGE BOOK]
Common Name English
NSC-521760
Code English
AMIFAMPRIDINE [INN]
Common Name English
PYRIDINE, 3,4-DIAMINO-
Systematic Name English
DAP
Common Name English
AMIFAMPRIDINE [MART.]
Common Name English
3,4-DIAMINOPYRIDINE
Systematic Name English
AMIFAMPRIDINE [USAN]
Common Name English
3,4 DIAMINOPYRIDINE [VANDF]
Common Name English
3,4-DAP
Code English
DYNAMINE
Brand Name English
AMIFAMPRIDINE [WHO-DD]
Common Name English
RUZURGI
Brand Name English
AMIFAMPRIDINE [EMA EPAR]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 56090
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
WHO-ATC N07XX05
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
WHO-VATC QN07XX05
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
NDF-RT N0000192795
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
FDA ORPHAN DRUG 299909
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
NCI_THESAURUS C93038
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
FDA ORPHAN DRUG 43189
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
FDA ORPHAN DRUG 556516
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
EMA ASSESSMENT REPORTS FIRDAPSE (AUTHORIZED: LAMBERT-EATON MYASTHENIC SYNDROME)
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
FDA ORPHAN DRUG 51590
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL354077
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
RXCUI
2106338
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-220-9
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
FDA UNII
RU4S6E2G0J
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
NCI_THESAURUS
C82687
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
WIKIPEDIA
3,4-DIAMINOPYRIDINE
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
IUPHAR
8032
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
EVMPD
SUB28846
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
LACTMED
Amifampridine
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
MESH
C016361
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
MERCK INDEX
M1668
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY Merck Index
CAS
54-96-6
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
INN
8804
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
EPA CompTox
54-96-6
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
PUBCHEM
5918
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
DRUG CENTRAL
4336
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY
DRUG BANK
DB11640
Created by admin on Sat Jun 26 06:11:22 UTC 2021 , Edited by admin on Sat Jun 26 06:11:22 UTC 2021
PRIMARY