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

Details

Stereochemistry ACHIRAL
Molecular Formula C5H6N2.ClH
Molecular Weight 130.575
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of 4-Aminopyridine hydrochloride

SMILES

Cl.NC1=CC=NC=C1

InChI

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

HIDE SMILES / InChI

Molecular Formula C5H6N2
Molecular Weight 94.1145
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including 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
195.0 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

2010
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: Page: p.3
unhealthy, 52.1 ± 8.8
n = 269
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 52.1 ± 8.8
Sex: M+F
Population Size: 269
Sources: Page: p.3
Disc. AE: Seizure, Myocardial infarction...
AEs leading to
discontinuation/dose reduction:
Seizure (1.1%)
Myocardial infarction (1.1%)
Sources: Page: p.3
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
Disc. AE: Weakness, Consciousness decreased...
AEs leading to
discontinuation/dose reduction:
Weakness
Consciousness decreased
Memory loss
Hypophonia
Structural brain disorders NEC
Sources: Page: p.3
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Sex: F
Population Size: 1
Sources: Page: p.3
Disc. AE: Complex partial seizures, Confusion...
AEs leading to
discontinuation/dose reduction:
Complex partial seizures
Confusion
Sources: Page: p.3
60 mg single, oral
Overdose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
Disc. AE: Mental state abnormal...
AEs leading to
discontinuation/dose reduction:
Mental state abnormal
Sources: Page: p.3
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: Page: p.2
unhealthy
n = 400
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 400
Sources: Page: p.2
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: Page: p.2
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.1
Disc. AE: Seizures...
AEs leading to
discontinuation/dose reduction:
Seizures
Sources: Page: p.1
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: Page: p.3
unhealthy, 52.1 ± 8.8
n = 269
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 52.1 ± 8.8
Sex: M+F
Population Size: 269
Sources: Page: p.3
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: Page: p.3
unhealthy, 52.1 ± 8.8
n = 269
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 52.1 ± 8.8
Sex: M+F
Population Size: 269
Sources: Page: p.3
Consciousness decreased Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
Hypophonia Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
Memory loss Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
Structural brain disorders NEC Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
Weakness Disc. AE
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
Complex partial seizures Disc. AE
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Sex: F
Population Size: 1
Sources: Page: p.3
Confusion Disc. AE
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Sex: F
Population Size: 1
Sources: Page: p.3
Mental state abnormal Disc. AE
60 mg single, oral
Overdose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources: Page: p.3
unhealthy
n = 1
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 1
Sources: Page: p.3
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: Page: p.2
unhealthy
n = 400
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 400
Sources: Page: p.2
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: Page: p.2
unhealthy
n = 400
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 400
Sources: Page: p.2
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: Page: p.2
unhealthy
n = 400
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 400
Sources: Page: p.2
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: Page: p.2
unhealthy
n = 400
Health Status: unhealthy
Condition: Multiple sclerosis
Population Size: 400
Sources: Page: p.2
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.1
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
The effects of quinine and 4-aminopyridine on conditioned place preference and changes in motor activity induced by morphine in rats.
1999 May
KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels.
2000 Jun
Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA).
2000 Mar 1
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
Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice.
2001 Apr 12
Effects of phosphodiesterase inhibitors on hypoxic pulmonary vasoconstriction. Influence of K(+) channels and nitric oxide.
2001 Apr 6
Syntheses of the first amine-dicarboxyboranes and their bis(methylester) and bis(N-ethylamide) derivatives.
2001 Apr 9
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
Nitrooxy alkyl apovincaminate activates K+ currents in rat neocortical neurons.
2001 Feb
Pharmacological properties of excitation-contraction mechanisms in isolated mouse left atria.
2001 Feb
Theta-frequency bursting and resonance in cerebellar granule cells: experimental evidence and modeling of a slow k+-dependent mechanism.
2001 Feb 1
The effect of acidosis on the ECG of the rat heart.
2001 Jan
Three types of K(+) currents in murine osteocyte-like cells (MLO-Y4).
2001 Jan
Modulation of Ca(2+) signaling by K(+) channels in a hypothalamic neuronal cell line (GT1-1).
2001 Jan
Dendritic coincidence detection of EPSPs and action potentials.
2001 Jan
Two kinds of transient outward currents, I(A) and I(Adepol), in F76 and D1 soma membranes of the subesophageal ganglia of Helix aspersa.
2001 Jan 1
Development and validation of a capillary electrophoresis assay for the determination of 3,4-diaminopyridine and 4-aminopyridine including related substances.
2001 Jan 12
Neurogenic bladder in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine.
2001 Jan 15
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
KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1.
2001 Jul
Role of K+ -channels in homotaurine-induced analgesia.
2001 Jun
Focal cooling rapidly terminates experimental neocortical seizures.
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
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
Potassium channel blocker TEA prevents CA1 hippocampal injury following transient forebrain ischemia in adult rats.
2001 Jun 8
The effects of different 4-aminopyridine and morphine combinations on the intensity of morphine abstinence.
2001 Mar
Synaptic and nonsynaptic contributions to giant ipsps and ectopic spikes induced by 4-aminopyridine in the hippocampus in vitro.
2001 Mar
Modulation of voltage-dependent K+ channel current in vascular smooth muscle cells from rat mesenteric arteries.
2001 Mar 15
Effects of pituitary adenylate cyclase activating polypeptide on lumbosacral preganglionic neurons in the neonatal rat spinal cord.
2001 Mar 23
Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle.
2001 Mar 9
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
Stretch-dependent potassium channels in murine colonic smooth muscle cells.
2001 May 15
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 12:36:18 GMT 2023
Edited
by admin
on Sat Dec 16 12:36:18 GMT 2023
Record UNII
897AWS9WZQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
4-Aminopyridine hydrochloride
Systematic Name English
PYRIDINE, 4-AMINO-, HYDROCHLORIDE
Systematic Name English
4-Pyridinamine, monohydrochloride
Systematic Name English
NSC-206404
Code English
4-Pyridinamine, hydrochloride (1:1)
Systematic Name English
Pyridin-4-amine hydrochloride
Systematic Name English
Code System Code Type Description
FDA UNII
897AWS9WZQ
Created by admin on Sat Dec 16 12:36:18 GMT 2023 , Edited by admin on Sat Dec 16 12:36:18 GMT 2023
PRIMARY
EPA CompTox
DTXSID70143115
Created by admin on Sat Dec 16 12:36:18 GMT 2023 , Edited by admin on Sat Dec 16 12:36:18 GMT 2023
PRIMARY
NSC
206404
Created by admin on Sat Dec 16 12:36:18 GMT 2023 , Edited by admin on Sat Dec 16 12:36:18 GMT 2023
PRIMARY
CAS
1003-40-3
Created by admin on Sat Dec 16 12:36:18 GMT 2023 , Edited by admin on Sat Dec 16 12:36:18 GMT 2023
PRIMARY
PUBCHEM
164772
Created by admin on Sat Dec 16 12:36:18 GMT 2023 , Edited by admin on Sat Dec 16 12:36:18 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE