Amifampridine (3,4-Diaminopyridine) 是一种口服有效和可透过细胞的电压门控钾 (Kv) 通道阻断剂 (PCB)。Amifampridine 对 BoNT/A (HY-P79153) 中毒有明显的逆转作用。Amifampridine 可增加神经肌肉连接 (NMJs) 的递质释放。Amifampridine 可用于 Lambert-Eaton 肌无力综合征 (LEMS) 的研究。
| 生物活性 | Amifampridine (3,4-Diaminopyridine) is an orally active, potent and cell permeablevoltage-gated potassium (Kv) channelblocker (PCB). Amifampridine is efficacy in the reversal ofBoNT/A(HY-P79153) intoxication. Amifampridine increases transmitter release from neuromuscular junctions (NMJs). Amifampridine can be used for Lambert-Eaton myasthenic syndrome (LEMS) research[1][2][3]. |
体外研究
(In Vitro) | Amifampridine (1.5 μM) significantly reduces Kv3.3 and Kv3.4 currents by about 10% in HEK293T cells, has no effect on Cav2.1 or Cav1.2 current[3].
Amifampridine (0-100 μM) increases the duration of the presynaptic AP (action potential) waveform at mammalian and frog NMJs in a dose-dependent manner[3].
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体内研究
(In Vivo) | Amifampridine (Oral gavage; 10 mg/kg; once) can antagonize muscle paralysis following BoNT/A intoxication[2].
Amifampridine (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 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) | | t1/2(h) | 1.04 | 1.28 | | AUC0-24(μM·h) | 4.29 | 9.72 | | F (%) | 100 | 56.7 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 38 mg/mL(348.21 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 9.1634 mL | 45.8169 mL | 91.6338 mL | | 5 mM | 1.8327 mL | 9.1634 mL | 18.3268 mL | | 10 mM | 0.9163 mL | 4.5817 mL | 9.1634 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (22.91 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (22.91 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (22.91 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (22.91 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (22.91 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (22.91 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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