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

Details

Stereochemistry ACHIRAL
Molecular Formula C5H6N2
Molecular Weight 94.1147
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DALFAMPRIDINE

SMILES

c1c[nH]ccc1=N

InChI

InChIKey=NUKYPUAOHBNCPY-UHFFFAOYSA-N
InChI=1S/C5H6N2/c6-5-1-3-7-4-2-5/h1-4H,(H2,6,7)

HIDE SMILES / InChI

Description
Curator's Comment:: https://www.drugs.com/cdi/dalfampridine.html | https://clinicaltrials.gov/ct2/show/NCT01356940 | https://www.ncbi.nlm.nih.gov/pubmed/22497693 | https://www.ncbi.nlm.nih.gov/pubmed/15084131

Dalfampridine is a potassium channel blocker, used as a research tool in characterizing subtypes of the potassium channel. Dalfampridine has also been used as a drug, to manage some of the symptoms of multiple sclerosis, and is indicated for symptomatic improvement of walking in adults with several variations of the disease. The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated. Dalfampridine is a broad spectrum potassium channel blocker. In animal studies, dalfampridine has been shown to increase conduction of action potentials in demyelinated axons through inhibition of potassium channels.

Originator

Sources: Zhurnal Russkago Fiziko-Khimicheskago Obshchestva (1915), 47, 835-8.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
195 µM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AMPYRA

Approved Use

AMPYRA (dalfampridine) is indicated as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed [see Clinical Studies (14)

Launch Date

1264118400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
23.77 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DALFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
246.48 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DALFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.16 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DALFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
97%
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DALFAMPRIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy, 52.1 ± 8.8
Health Status: unhealthy
Age Group: 52.1 ± 8.8
Sex: M+F
Sources:
Disc. AE: Seizure, Myocardial infarction...
AEs leading to
discontinuation/dose reduction:
Seizure (1.1%)
Myocardial infarction (1.1%)
Sources:
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
unhealthy
Disc. AE: Weakness, Consciousness decreased...
AEs leading to
discontinuation/dose reduction:
Weakness
Consciousness decreased
Memory loss
Hypophonia
Structural brain disorders NEC
Sources:
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
Disc. AE: Complex partial seizures, Confusion...
AEs leading to
discontinuation/dose reduction:
Complex partial seizures
Confusion
Sources:
60 mg single, oral
Overdose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
unhealthy
Disc. AE: Mental state abnormal...
AEs leading to
discontinuation/dose reduction:
Mental state abnormal
Sources:
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Headache, Balance disorder...
AEs leading to
discontinuation/dose reduction:
Headache (0.5%)
Balance disorder (0.5%)
Dizziness (0.5%)
Confusional state (0.5%)
Sources:
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Seizures...
AEs leading to
discontinuation/dose reduction:
Seizures
Sources:
AEs

AEs

AESignificanceDosePopulation
Myocardial infarction 1.1%
Disc. AE
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy, 52.1 ± 8.8
Health Status: unhealthy
Age Group: 52.1 ± 8.8
Sex: M+F
Sources:
Seizure 1.1%
Disc. AE
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy, 52.1 ± 8.8
Health Status: unhealthy
Age Group: 52.1 ± 8.8
Sex: M+F
Sources:
Consciousness decreased Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
unhealthy
Hypophonia Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
unhealthy
Memory loss Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
unhealthy
Structural brain disorders NEC Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
unhealthy
Weakness Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
unhealthy
Complex partial seizures Disc. AE
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
Confusion Disc. AE
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
Mental state abnormal Disc. AE
60 mg single, oral
Overdose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
unhealthy
Balance disorder 0.5%
Disc. AE
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
Confusional state 0.5%
Disc. AE
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
Dizziness 0.5%
Disc. AE
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
Headache 0.5%
Disc. AE
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
Seizures Disc. AE
10 mg 2 times / day multiple, oral
Recommended
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak [IC50 195 uM]
weak [IC50 270 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
minor
minor
minor
minor
minor
minor
minor
minor
minor
minor
minor
no
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Treatment of the neuromuscular junction with 4-aminopyridine results in improved reinnervation following nerve injury in neonatal rats.
2001
The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1.
2001 Apr
Differential expression of KV and KCa channels in vascular smooth muscle cells during 1-day culture.
2001 Apr
Calcium dynamics and electrophysiological properties of cerebellar Purkinje cells in SCA1 transgenic mice.
2001 Apr
Presynaptic N-methyl-D-aspartate receptor activation inhibits neurotransmitter release through nitric oxide formation in rat hippocampal nerve terminals.
2001 Apr 18
Syntheses of the first amine-dicarboxyboranes and their bis(methylester) and bis(N-ethylamide) derivatives.
2001 Apr 9
A model for 4-aminopyridine action on K channels: similarities to tetraethylammonium ion action.
2001 Aug
Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and potassium channels.
2001 Aug
The relaxation induced by S-nitroso-glutathione and S-nitroso-N-acetylcysteine in rat aorta is not related to nitric oxide production.
2001 Aug
Chloride distribution in the CA1 region of newborn and adult hippocampus by light microscopic histochemistry.
2001 Feb
Nitrooxy alkyl apovincaminate activates K+ currents in rat neocortical neurons.
2001 Feb
The effect of acidosis on the ECG of the rat heart.
2001 Jan
Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries.
2001 Jul
Imaging of 4-AP-induced, GABA(A)-dependent spontaneous synchronized activity mediated by the hippocampal interneuron network.
2001 Jul
KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1.
2001 Jul
Long-term recordings of networks of immortalized GnRH neurons reveal episodic patterns of electrical activity.
2001 Jul
Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells.
2001 Jul
Gap junctions synchronize the firing of inhibitory interneurons in guinea pig hippocampus.
2001 Jul 13
Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve terminals (synaptosomes) by suppression of voltage-activated calcium channel activity.
2001 Jul 20
Role of K+ -channels in homotaurine-induced analgesia.
2001 Jun
Normal coordinate analysis of 4-aminopyridine. Effect of substituent on pyridine ring in metal complexes of 4-substituted pyridines.
2001 Jun
Focal cooling rapidly terminates experimental neocortical seizures.
2001 Jun
Pharmacological modulation of SK3 channels.
2001 Jun
Tonotopic map of potassium currents in chick auditory hair cells using an intact basilar papilla.
2001 Jun
Alterations in a redox oxygen sensing mechanism in chronic hypoxia.
2001 Jun
Superfusion of synaptosomes to study presynaptic mechanisms involved in neurotransmitter release from rat brain.
2001 Jun
Synchronized Ca2+ signals mediated by Ca2+ action potentials in the hippocampal neuron network in vitro.
2001 Jun
Potassium channels regulate tone in rat pulmonary veins.
2001 Jun
Mechanisms underlying presynaptic facilitatory effect of cyclothiazide at the calyx of Held of juvenile rats.
2001 Jun 1
Functional and molecular expression of a voltage-dependent K(+) channel (Kv1.1) in interstitial cells of Cajal.
2001 Jun 1
Skin surface electric potential induced by ion-flux through epidermal cell layers.
2001 Jun 1
Dopamine D4 receptor-deficient mice display cortical hyperexcitability.
2001 Jun 1
Membrane resonance and subthreshold membrane oscillations in mesencephalic V neurons: participants in burst generation.
2001 Jun 1
Theoretical analysis of the molecular determinants responsible for the K(+) channel blocking by aminopyridines.
2001 Jun 15
"Use-dependent" effects of cisapride on postrest action potentials in rabbit ventricular myocardium.
2001 Jun 22
Developmental characteristics of epileptiform activity in immature rat neocortex: a comparison of four in vitro seizure models.
2001 Jun 29
Potassium channel blocker TEA prevents CA1 hippocampal injury following transient forebrain ischemia in adult rats.
2001 Jun 8
Anticonvulsant properties and bio-guided isolation of palmitone from leaves of Annona diversifolia.
2001 Mar
Modulation of voltage-dependent K+ channel current in vascular smooth muscle cells from rat mesenteric arteries.
2001 Mar 15
Influence of admixed carboxymethylcellulose on release of 4-aminopyridine from hydroxypropyl methylcellulose matrix tablets.
2001 Mar 23
Time-dependent distribution and neuronal localization of c-fos protein in the rat hippocampus following 4-aminopyridine seizures.
2001 May
Sites and ionic mechanisms of hypoxic vasoconstriction in frog skin.
2001 May
A redox-based mechanism for the contractile and relaxing effects of NO in the guinea-pig gall bladder.
2001 May 1
Targeted replacement of KV1.5 in the mouse leads to loss of the 4-aminopyridine-sensitive component of I(K,slow) and resistance to drug-induced qt prolongation.
2001 May 11
Stretch-dependent potassium channels in murine colonic smooth muscle cells.
2001 May 15
Oxygen dilation in fetal pulmonary arterioles: role of K(+) channels.
2001 May 15
Inhibition of glutamate release by BIA 2-093 and BIA 2-024, two novel derivatives of carbamazepine, due to blockade of sodium but not calcium channels.
2001 May 15
minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel?
2001 May 25
Ion channels associated with the ectopic discharges generated after segmental spinal nerve injury in the rat.
2001 May 4
BTS 72664-- a novel CNS drug with potential anticonvulsant, neuroprotective, and antimigraine properties.
2001 Summer
Patents

Sample Use Guides

The maximum recommended dose of AMPYRA is one 10 mg tablet twice daily, taken with or without food, and should not be exceeded.
Route of Administration: Oral
At DIV25, the differentiating cells were re-seeded to Matrigel coated 12-mm glass coverslips in densities of 400,000 cells per well. Media was replaced completely the next day by fresh maturation media. Media containing either 100 mM 4-Aminopyridine diluted in DMSO or the equivalent amount DMSO only was given to the cells 72 hours before the start of week 7 (DIV42) and lasted until the cells were analyzed during week 7. Half the media was replaced every third day. Final electrophysiological recordings of the treated vs. non-treated cells rigorously were taken in pairs of one treated and one nontreated coverslip within a time frame of 48 hours.
Name Type Language
DALFAMPRIDINE
DASH   HSDB   II   MI   ORANGE BOOK   USAN   USP-RS   VANDF  
USAN  
Official Name English
FAMPRIDINE [INN]
Common Name English
DALFAMPRIDINE [HSDB]
Common Name English
FAMPRIDINE
EMA EPAR   INN   MART.   VANDF   WHO-DD  
INN  
Official Name English
DALFAMPRIDINE [II]
Common Name English
DALFAMPRIDINE [MI]
Common Name English
4-AP
Common Name English
FAMPRIDINE [MART.]
Common Name English
DALFAMPRIDINE [ORANGE BOOK]
Common Name English
AMPYRA
Brand Name English
DALFAMPRIDINE [USAN]
Common Name English
FAMPRIDINE [WHO-DD]
Common Name English
DALFAMPRIDINE [VANDF]
Common Name English
PYRIDIN-4-AMINE
Systematic Name English
DALFAMPRIDINE [USP MONOGRAPH]
Common Name English
FAMPRIDINE (4-AMINOPYRIDINE) [VANDF]
Common Name English
DALFAMPRIDINE [USP-RS]
Common Name English
4-PYRIDINAMINE
Systematic Name English
FAMPRIDINE [VANDF]
Common Name English
FAMPRIDINE [EMA EPAR]
Common Name English
4-AMINOPYRIDINE
Systematic Name English
EL-970
Code English
NSC-15041
Code English
FAMPYRA
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C93038
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
FDA ORPHAN DRUG 18186
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
FDA ORPHAN DRUG 214205
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
FDA ORPHAN DRUG 104497
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
EMA ASSESSMENT REPORTS FAMPYRA (AUTHORIZED: MULTIPLE SCLEROSIS)
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
EU-Orphan Drug EU/3/07/458
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
NDF-RT N0000192795
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
FDA ORPHAN DRUG 713019
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
LIVERTOX 259
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
WHO-ATC N07XX07
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
WHO-VATC QN07XX07
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
EPA PESTICIDE CODE 69201
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
Code System Code Type Description
INN
7283
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
PUBCHEM
1727
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
MERCK INDEX
M4072
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY Merck Index
HSDB
6037
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
IUPHAR
2416
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
DRUG CENTRAL
4163
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
NCI_THESAURUS
C76777
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
EPA CompTox
504-24-5
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
LACTMED
Dalfampridine
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
CAS
504-24-5
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
ECHA (EC/EINECS)
207-987-9
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
USP_CATALOG
1162454
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY USP-RS
MESH
D015761
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
FDA UNII
BH3B64OKL9
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
EVMPD
SUB07505MIG
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
DRUG BANK
DB06637
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
WIKIPEDIA
4-AMINOPYRIDINE
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
ChEMBL
CHEMBL284348
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY
RXCUI
897018
Created by admin on Sat Jun 26 07:05:38 UTC 2021 , Edited by admin on Sat Jun 26 07:05:38 UTC 2021
PRIMARY RxNorm