Amifampridine
Amifampridine primarily improves muscle functioning by increasing acetylcholine in the neuromuscular junction.[1][2] Common brand names are Firdapse or Ruzurgi.[3]
Theory
Amifampridine, also known as 3,4-diaminopyridine or 3,4-DAP, belongs to the group of aminopyridines and is used in conditions where acetylcholine release is reduced, e.g., for treating Lambert-Eaton Myasthenic Syndrome (LEMS) as an orphan drug. It belongs to the category of potassium channel blockers and is closely related to fampridine, a drug used in multiple sclerosis to improve cognitive functioning and cognitive fatigue.[1] Another drug seeking to increase the amount of acetylcholine in the neuromuscular junction is pyridostigmine.
Mechanism
Peripheral Effects
Amifampridine blocks the voltage-gated potassium channels and thus, potassium release. Thus, the nerve terminal remains in a depolarized state for a longer period of time which allows a longer opening of calcium channels releasing calcium ions into the presynaptic terminal. In turn, this triggers an increased release of neurotransmitters into the synaptic cleft, such as acetylcholine. Acetylcholine causes a muscle to contract and more acetylcholine activates muscle receptors more strongly, thereby improving muscle function.[1]
Brainstem
Theoretically, amifampridine can also act in the brainstem. Regarding its use in LEMS, this is clinically irrelevant except for side effects which can be minimized by adequate dosage. The presynaptic potassium channels affected in the peripheral nervous system also exist in the neurons of the central nervous system, including the brainstem which, among others, controls respiration, cardiovascular function, and alertness, and blockage of potassium channels can increase neurotransmitter release there as well. Based on animal studies, potassium channel blockers may alter neuronal excitability or reflexes.[2]
Evidence
In a case report on five patients, it reduced fatigue and excessive sleep duration while improving cognitive functioning in post-covid syndrome. Illness duration prior to treatment ranged from 4 to 14 months. Overall, a significant increase in Bell score was observed and confirmed by a double blinded discontinuation trial in two patients. [1]
Risks and safety
See also
Learn more
WebMD: https://www.webmd.com/drugs/firdapse-amifampridine
Wikipedia: https://en.wikipedia.org/wiki/Amifampridine
References
- ↑ 1.0 1.1 1.2 1.3 Boehmeke, Thomas (2024). "Reduced Fatigue Symptoms in the Post-COVID Syndrome With Amifampridine: A Collective Casuistry With Double-Blind Discontinuation Trials" (PDF). Cureus. 16 (1).
- ↑ 2.0 2.1 Strupp, T; Teufel, J; Zwergal, A; Schniepp, R (2017). "Aminopyridines for the treatment of neurologic disorders". Neurol Clin Pract. 7 (1).
- ↑ WebMD. "Firdapse(amifampridine): Uses, Side Effects, Interactions".
