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AMifaMpridine Phosphate

Product NameAMifaMpridine Phosphate
CAS446254-47-3
MFC5H10N3O4P
MW207.124361
EINECS
MOL File446254-47-3.mol

Usage And Synthesis

Uses

Amifampridine (3,4-Diaminopyridine) phosphate is an orally active, potent and cell permeable voltage-gated potassium (Kv) channel blocker (PCB). Amifampridine phosphate is efficacy in the reversal of BoNT/A (HY-P79153) intoxication. Amifampridine phosphate increases transmitter release from neuromuscular junctions (NMJs). Amifampridine phosphate can be used for Lambert-Eaton myasthenic syndrome (LEMS) research[1][2][3].

in vivo

Amifampridine phosphate (Oral gavage; 10 mg/kg; once) can antagonize muscle paralysis following BoNT/A intoxication^[2].
Amifampridine phosphate (2.5 mg/kg (IV); 10 mg/kg (PO); once) shows 1 hour plasma half-life and about 57% bioavailability (F) in mice^[2].
Amifampridine phosphate has a short plasma half-life and can induce seizures when present at high concentrations, following penetration of the blood-brain barrier^[2].

Animal Model:	CD-1 mouse (female,25 g, 6 weeks old)^[2]
Dosage:	10 mg/kg
Administration:	Oral gavage, once, after BoNT/A administration (IP)
Result:	Revealed that neither LEMs alone (182 ± 43 min) nor the maximum safe orally deliverable dose of 3,4-DAP alone (225 ± 24 min) could significantly increase the time to death following toxin administration (216 ± 29 min). However, when the 10/50/40 3,4-DAP/LEM/shellac formulation was administered at 25 mg/kg the time to death was 302 ± 26 min - a 40% increase as compared to toxin alone.

Animal Model:

CD-1 mouse (30-35 g, 8 weeks old)^[2]

Dosage:

2.5 mg/kg (IV); 10 mg/kg (PO)

Administration:

IV, orally, once (Pharmacokinetic Analysis)

Result:

Pharmacokinetic Parameters of Amifampridine in CD-1 mouse^[1].

	IV (2.5 mg/kg)	PO (10 mg/kg)
t_1/2 (h)	1.04	1.28
AUC_0-24 (μM·h)	4.29	9.72
F (%)	100	56.7

References

[1] Maarten J Titulaer, et al. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011 Dec;10(12):1098-107. DOI:10.1016/S1474-4422(11)70245-9
[2] T L Harris, et al. Lycopodium clavatum exine microcapsules enable safe oral delivery of 3,4-diaminopyridine for treatment of botulinum neurotoxin A intoxication. Chem Commun (Camb). 2016 Mar 18;52(22):4187-90. DOI:10.1039/c6cc00615a
[3] Ojala KS, et al. A high-affinity, partial antagonist effect of 3,4-diaminopyridine mediates action potential broadening and enhancement of transmitter release at NMJs. J Biol Chem. 2021 Jan-Jun;296:100302. DOI:10.1016/j.jbc.2021.100302

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