THERAPY DOSSIER · th-c1db12757044

4-Aminopyridine

Drug · Voltage-gated potassium channel blocker (BLOCKER, direct interaction)

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This record is classified as “NO TRAUMA TRANSLATION”. Read the indication and notes below for the specific context.

Evidence & regulatory context

Mechanism: Voltage-gated potassium channel blocker (BLOCKER, direct interaction)
Target: CHEMBL2362996
Injury models: Crush · Spinal cord injury
Reported indication: Improvement of walking in multiple sclerosis (K+ channel blocker; dalfampridine/Ampyra, approved 2010)
First approval: 2010
Development stage: Approved for MS walking; peripheral-nerve-injury use terminated
ChEMBL record: CHEMBL284348 ↗
ChEMBL max phase: 4 / 4 (development scale, not regulatory approval)
Synonyms: Dalfampridine; Fampridine; 4-aminopyridine; Ampyra; Fampyra; EL-970; NSC-15041
Note: Not recorded

Clinical trials 8

1 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

NCT04026568 ↗Injury indicationPHASE2/PHASE3terminated

A Single Dose Pharmaco-Diagnostic for Peripheral Nerve Continuity After Trauma (4-Aminopyridine)

Nerve Injury

Enrolment: 1 · Results not recorded

NCT02143167 ↗PHASE4completed

Combination of Resistance Training and Prolonged Release Fampridine in Multiple Sclerosis (RETRAP)

Multiple Sclerosis

Enrolment: 40 · Results not recorded

NCT02146534 ↗PHASE4completed

Prolonged-release Fampridine as Adjunct Therapy to Active Motor Training in MS Patients

Multiple Sclerosis

Enrolment: 44 · Results not recorded

NCT00654927 ↗PHASE3completed

Phase 3 Open-Label Extension of Oral Fampridine-SR in Multiple Sclerosis

Multiple Sclerosis

Enrolment: 177 · Results not recorded

NCT00483652 ↗PHASE3completed

Double-Blind Placebo-Controlled Study of Oral Fampridine-SR 10 mg b.i.d. in Multiple Sclerosis

Multiple Sclerosis

Enrolment: 240 · Results not recorded

NCT01337986 ↗PHASE2/PHASE3completed

Dalfampridine After Optic Neuritis to Improve Visual Function in Multiple Sclerosis

Multiple Sclerosis · Optic Neuritis

Enrolment: 53 · Results not recorded

NCT01645787 ↗PHASE2/PHASE3completed

Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent

Spinal Muscular Atrophy

Enrolment: 11 · Results not recorded

NCT01532154 ↗NAterminated

Fampridine Pregnancy Exposure Registry

Multiple Sclerosis · Pregnancy

Enrolment: 1 · Results not recorded

Preclinical evidence 6

4 studies reported at therapy level; 6 evidence entries itemised.

PMID 30901424 ↗2019Reported benefit

4-Aminopyridine as a Single Agent Diagnostic and Treatment for Severe Nerve Crush Injury.

MouseCrushPeripheral-nerve crushSustained early administration after injury

Model: Standard mouse models of traumatic peripheral nerve injury, including severe nerve crush and gap lesions

Sustained early 4-AP administration increased the speed and extent of behavioural recovery more rapidly than could be explained by axonal regeneration, enhanced recovery of nerve conduction velocity, promoted remyelination and increased post-injury axonal area. It also allowed rapid discrimination…

Extraction: extract · Subtype source: rule · Supplied extraction confidence: 0.6. Machine-extracted fields require source verification.

PMID 27861125 ↗2016Reported benefit

4-Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury.

MouseCrushPeripheral-nerve crushC57BL/6Femalen = Minimum of 5 and generally 8 mice per group, experiments re…Intraperitoneal for systemic dosing; local implantation of 4-AP-PLGA carriers in PEG hydrogel at the crush site10 ug per day systemically; local PLGA microparticles conta…First dose 24 h after injury

Model: Sciatic nerve crush injury (30 s crush); nerve transection and sham surgery also used

Daily 4-aminopyridine started 24 h after sciatic crush accelerated gait recovery, improved nerve conduction velocity and increased remyelination and axonal area without worsening neuropathic pain.

Extraction: extract · Subtype source: rule · Supplied extraction confidence: 0.9. Machine-extracted fields require source verification.

PMID 21988176 ↗2011Reported benefit

Paranodal myelin damage after acute stretch in Guinea pig spinal cord.

Guinea pigSpinal cord injuryDistractionFemaleApplied after stretch injury, to test restoration of conduction

Model: Acute mechanical stretch injury of isolated guinea pig spinal cord (white matter), causing paranodal myelin disruption and axonal conduction failure

Anatomical evidence showed paranodal myelin disruption with exposure and redistribution of potassium channels and paranodal myelin decompaction after mechanical insult, arising from both the initial physical impact and secondary calcium-dependent biochemical reactions. 4-Aminopyridine partially res…

Extraction: extract · Subtype source: llm · Supplied extraction confidence: 0.65. Machine-extracted fields require source verification.

PMID 29228863 ↗2018Reported benefit

Parallel Evaluation of Two Potassium Channel Blockers in Restoring Conduction in Mechanical Spinal Cord Injury in Rat.

RatSpinal cord injuryUnspecifiedSprague-DawleyMaleIntraperitoneal4-AP-3-MeOH 1 and 5 mg/kg; 4-AP 1 mg/kgApplied in rats 2 weeks after spinal cord injury

Model: Mechanical spinal cord injury, ex vivo and in vivo

4-AP-3-MeOH produced significantly greater augmentation of axonal conduction than 4-AP in both acute and chronic injury without reducing responsiveness to multiple stimuli, was tolerated at a dose at least 5 times higher than 4-AP, improved motor function at 5 mg/kg, and both agents alleviated neur…

Extraction: extract · Supplied extraction confidence: 0.75. Machine-extracted fields require source verification.

PMID 9417828 ↗1997

Conduction block in acute and chronic spinal cord injury: different dose-response characteristics for reversal by 4-aminopyridine

Guinea pigSpinal cord injury

Extraction: mesh. Machine-extracted fields require source verification.

PMID 7660281 ↗1995

Effect of 4-aminopyridine in acute spinal cord injury

RatSpinal cord injury

Extraction: mesh. Machine-extracted fields require source verification.

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