ContaminantDB: 4-Aminopyridine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (17)XML

Record Information

Version

1.0

Creation Date

2009-07-05 02:42:53 UTC

Update Date

2026-03-26 20:10:17 UTC

Accession Number

CHEM002080

Identification

Common Name

4-Aminopyridine

Class

Small Molecule

Description

Dalfampridine is a potassium channel blocker used to help multiple sclerosis patients walk. This is the first drug that was specifically approved to help with mobility in these patients. FDA approved on January 22, 2010. 4-Aminopyridine is an organic compound with the formula H2NC5H4N. The molecule is one of the three isomeric amines of pyridine. 4-Aminopyridine (4-AP) is prepared by the decarbonylation of pyridine-4-carboxyamide using sodium hypochlorite via the Hofmann rearrangement (7).

Contaminant Sources

Clean Air Act Chemicals
HPV EPA Chemicals
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Amine
Drug
Industrial Precursor/Intermediate
Organic Compound
Potassium Channel Blocker
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
4-AP	ChEBI
4-Pyridinamine	ChEBI
4-Pyridylamine	ChEBI
Ampyra	ChEBI
Avitrol	ChEBI
Fampridina	ChEBI
Fampridine	ChEBI
Fampridinum	ChEBI
gamma-Aminopyridine	ChEBI
N07XX07	ChEBI
p-Aminopyridine	ChEBI
4-Aminopyridine	Kegg
Neurelan	Kegg
Fampyra	Kegg
g-Aminopyridine	Generator
Γ-aminopyridine	Generator
Dalfampridine	ChEBI
4 Aminopyridine	MeSH
4 Aminopyridine sustained release	MeSH
Pymadine	MeSH
Fampridine SR	MeSH
Fampridine-SR	MeSH
4-Aminopyridine sustained release	MeSH
VMI 103	MeSH
Sustained release, 4-aminopyridine	MeSH
VMI-103	MeSH

Chemical Formula

C₅H₆N₂

Average Molecular Mass

94.115 g/mol

Monoisotopic Mass

94.053 g/mol

CAS Registry Number

504-24-5

IUPAC Name

1,4-dihydropyridin-4-imine

Traditional Name

4-aminopyridine

SMILES

N=C1C=CNC=C1

InChI Identifier

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

InChI Key

NUKYPUAOHBNCPY-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as aminopyridines and derivatives. These are organic heterocyclic compounds containing an amino group attached to a pyridine ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Pyridines and derivatives

Sub Class

Aminopyridines and derivatives

Direct Parent

Aminopyridines and derivatives

Alternative Parents

Substituents

Aminopyridine
Heteroaromatic compound
Azacycle
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Primary amine
Organonitrogen compound
Amine
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

aromatic amine (CHEBI:34385 )
aminopyridine (CHEBI:34385 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

potassium channel blocker

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

Colourless solid (7).

Experimental Properties

Property	Value
Melting Point	157-161°C
Boiling Point	273°C
Solubility	74 g/L

Predicted Properties

Property	Value	Source
Water Solubility	6.73 g/L	ALOGPS
logP	-0.65	ALOGPS
logP	0.29	ChemAxon
logS	-1.2	ALOGPS
pKa (Strongest Acidic)	16.04	ChemAxon
pKa (Strongest Basic)	12.18	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	35.88 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	40.09 m³·mol⁻¹	ChemAxon
Polarizability	9.66 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0006-9000000000-d76cf775a4e0c55c9a50	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 5V, positive	splash10-0002-9000000000-38892360ceafd0620f65	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 7V, positive	splash10-0002-9000000000-51326f026124a275802e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 10V, positive	splash10-0002-9000000000-bdf16d24f7f300bcac20	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 15V, positive	splash10-0002-9000000000-5fc3bcf86f00669faf88	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 17V, positive	splash10-0002-9000000000-66e0f38bd0aab60037df	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 20V, positive	splash10-0002-9000000000-bcd6a6c53e7a2d9d3404	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 23V, positive	splash10-002b-9000000000-3fe4f715dfb6e091d719	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 25V, positive	splash10-002b-9000000000-a83c3015f770c5d5230b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 27V, positive	splash10-002b-9000000000-e6a43885cc1f15e8fa0c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 30V, positive	splash10-004j-9000000000-3ba9365c05683adc3067	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 33V, positive	splash10-0fba-9000000000-89b6856fba31c7af9858	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 35V, positive	splash10-0fb9-9000000000-28ffe5713230b691f900	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 40V, positive	splash10-0ufr-9000000000-0e5a60c0c7b08c359c50	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 45V, positive	splash10-0udi-9000000000-a46456374bb11088cf77	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 1V, positive	splash10-004i-9000000000-ddb0878d8656440d3615	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 2V, positive	splash10-004i-9000000000-2622d71d150ed8a3a352	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 3V, positive	splash10-004i-9000000000-2622d71d150ed8a3a352	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 4V, positive	splash10-004i-9000000000-2622d71d150ed8a3a352	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 5V, positive	splash10-004i-9000000000-2622d71d150ed8a3a352	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-9000000000-b9ca65a501bd24b8adf5	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-9000000000-5b9ddb3af3ab551845d8	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0v00-9000000000-68383f33699a6453bc49	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-9000000000-f240dc053a801a491f6c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9000000000-1b9fe497d4864ae333ef	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-002f-9000000000-ea15c905b0157a6e6115	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0006-9000000000-8298bac1cfd86955d1ee	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Inhalation (12, 9) ; oral (12, 9) ; dermal (12, 9) ; intravenous (12, 9) Orally-administered dalfampridine is rapidly and completely absorbed from the gastrointestinal tract. Tmax, immediate release form = 1 hour; Tmax, extended release form = 3.5 hours; Cmax, 10 mg extended release = 17.3 - 21.6 ng/mL; Relative bioavailability of 10 mg extended-release tablets compared to aqueous oral solution = 96%

Mechanism of Toxicity

4-Aminopyridine blocks potassium channels and thereby increases acetylcholine, and possibly noradrenaline, release at nerve terminals (1). In MS, axons are progressively demyelinated which exposes potassium channels. As a result, there is a leak of potassium ions which results in the repolarization of cells and a decrease in neuronal excitability. The overall impact is the impairment of neuromuscular transmission as it is harder to trigger an action potential. Dalfampridine inhibits voltage-gated potassium channels in the CNS to maintain the transmembrane potential and prolong action potential. In other words, dalfampridine works to make sure that the current available is high enough to stimulate conduction in demyelinated axons that are exposed in MS patients. Furthermore, it facilitates neuromuscular and synaptic transmission by relieving conduction blocks in demyelinated axons.

Metabolism

Not extensively metabolized by the liver therefore drugs effecting the cytochrome P450 enzyme system that are concomitantly administered with dalfampridine are not expected to interact with each other. 4-Aminopyridine is rapidly absorbed into the bloodstream from the gastrointestinal tract. It is readily broken down, or metabolized, in the liver into removable compounds excreted in urine. After intravenous and oral absoprtion, the metabolites were almost all excreted in the urine. It does not to concentrate or accumulate in skin. 4-Aminopyridine is excreted in urine and rapidly detoxified in the liver (11, 8). Metabolites include 3-hydroxy-4-aminopyridine and 3-hydroxy-4-aminopyridine sulfate and both are inactive. CYP2E1 is the enzyme responsible for 3-hydroxylation of dalfampridine. Route of Elimination: Almost all of the dose and its metabolites are completely eliminated by the kidneys after 24 hours. Urine (96%; 90% of total dose as unchanged drug); Feces (0.5%) Half Life: Immediate release form = 3.5 hours; Extended release form = 5.47 hours;

Toxicity Values

LD50, oral, mouse = 19 mg/kg LD50, oral, rat = 21 mg/kg LD50: 20-29 mg/kg (Oral, Rat) (8) LD50: 3.7 mg/kg (Oral, Dog) (8) LD50: 326 mg/kg (Dermal, Rabbit) (8)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Dalfampridine is a neurofunctional modifier that helps improve walking speed in patients with multiple sclerosis (MS). It is used primarily as a research tool, in characterizing subtypes of potassium channel, and has also been used to manage some of the symptoms of multiple sclerosis, for which it has orphan drug status in the United States and is undergoing Phase III clinical trials as of 2008 (7).

Minimum Risk Level

Not Available

Health Effects

Conditions associated with overdose have included parasthesias, seizures, and atrial fibrillation. Human systemic effects by ingestion include hallucinations and distorted perceptions, and dyspnea (7).

Symptoms

Local irritation on contact with the skin, mucous membranes and cornea. Symptoms floowing ingestion include vomiting, Weakness, dizziness, disorientation, hyperexcitability, tremors, periorbital paresthesias and tonic-clonic seizures may be noted (10, 12, 9).

Treatment

Administer charcoal as a slurry. Consider gastric lavage after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in Trendelenburg and left lateral decubitus position or by endotracheal intubation. Control any seizures first. Following inhalation, move patient to fresh air and monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If the exposure occurs through dermal exposure, remove contaminated clothing and wash exposed area thoroughly with soap and water. (10)

Concentrations

Not Available

External Links

DrugBank ID

DB06637

HMDB ID

Not Available

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Dalfampridine

Chemspider ID

Not Available

ChEBI ID

34385

PubChem Compound ID

1727

Kegg Compound ID

C13728

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Fabio GARAVAGLIA, Alessandro BAROZZA, Jacopo ROLETTO, Paolo PAISSONI, “ONE-POT PROCESS FOR THE SYNTHESIS OF DALFAMPRIDINE.” U.S. Patent US20110319628, issued December 29, 2011.