General
Preferred name
AMIFAMPRIDINE
Synonyms
3,4-Diaminopyridine ()
Pyridine-3,4-diamine ()
3,4-Pyridinediamine ()
AMIFAMPRIDINE PHOSPHATE ()
Amifampridine, pyridine-3,4-diamine ()
DAP ()
3,4-DAP ()
Dynamine ()
3,4-Diammoniopyridinium ()
Ruzurgi ()
NSC-521760 ()
4-DAP ()
DAPP ()
3,4-DAPP ()
Firdapse ()
Zenas ()
P&D ID
PD012714
CAS
54-96-6
Tags
available
drug
Approved by
EMA
FDA
First approval
2009
2018
Drug Status
investigational
approved
Drug indication
LambertEaton myasthenic syndrome
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION
Amifampridine is indicated for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults[F272] and in patients aged 6 to less than 17 years of age.[F4609,L6250] Nevertheless, it is important to note that at the current time only the Firdapse brand of amifampridine is indicated for the treatment of LEMS in adults[F272] and the Ruzurgi brand of amifampridine is indicated for the treatment of LEMS in patients aged 6 to less than 17 years.[F4609,L6250]
TOXICITY
The approximate oral LD50 was >25mg/kg in rats and 100 mg/kg in mice. The approximate intravenous LD50 was 25 mg/kg in both rats and mice [F273]. 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].
DESCRIPTION
Amifampridine is a potassium channel blocker.
(GtoPdb)
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].
DESCRIPTION
Amifampridine is a drug, predominantly in the treatment of a number of rare muscle diseases. It 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.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
17
BOC Sciences Bioactive Compounds
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine BioReference Compounds
Guide to Pharmacology
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
45
Molecular Weight
109.06
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
2
Rotatable Bonds
0
Ring Count
1
Aromatic Ring Count
1
cLogP
0.25
TPSA
64.93
Fraction CSP3
0.0
Chiral centers
0.0
Largest ring
6.0
QED
0.5
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Indication
Lambert-Eaton myasthenic syndrome (LEMS)
MOA
potassium channel blocker
Pathway
Membrane Transporter/Ion Channel
Target
Potassium Channel
Source data
