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Neurobiology of the Gustatory Zone of Nucleus Tractus Solitarius
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
These complex firing patterns are mediated by different ionic conductances. Ionic channel blockers have now been used to characterize the conductances involved in the intrinsic firing properties of rNTS neurons.19 Application of 4-aminopyridine, used to block K channels, results in reduction or elimination of the delay in firing of Group II neurons. Voltage-clamp recordings of Group II neurons reveal that the firing delay is due to a transient outward K+ current partially inactivated around the resting membrane potential and blocked by 4-aminopyridine (Figure 3). Hyperpolarization removes this inactivation causing a delay in the firing of the neuron. Based on its pharmacology and voltage dependence, this current is similar to the A-current (IKA) previously described in many other CNS neurons including the caudal NTS.20-23
Multiple Sclerosis and Related Conditions
Published in John W. Scadding, Nicholas A. Losseff, Clinical Neurology, 2011
The aminopyridines (4-aminopyridine (4-AP) and 3,4-diaminopyridine (3–4 DAP)) inhibit potassium channels and widen the nerve action potential, reversing conduction block in experimentally demyelinated axons. These agents act similarly on synaptic potassium channels. Their ability to reverse conduction block in fibres with a critically low safety factor has led to clinical studies in patients with MS, particularly those with severe and progressive disability in whom the symptoms show temperature dependence. 4-AP crosses the blood–brain barrier more easily, and has therefore been studied more intensively than 3–4 DAP. Both agents have a small but significant beneficial effect on disability, but their widespread use has been limited by a narrow therapeutic index. They are associated with significant side effects, including dizziness, paraesthesiae and abdominal pain. At higher doses, they may precipitate an encephalopathy or seizures. 4-AP is currently available for unlicensed treatment of highly selected patients. The drug is introduced at a low dose of 5 mg given once or twice daily, and dosage increments must be titrated carefully to a maximum dose of 10 mg taken three times daily. These practical difficulties with the use of potassium channel blockers have led to work using a slow release formulation of 4-AP, fampridine, and a recent trial suggested that the drug could be used relatively safely and that it was capable of improving gait in a subset of ambulant patients with established disability.
Multiple Sclerosis: Impact on Elderly People
Published in José León-Carrión, Margaret J. Giannini, Behavioral Neurology in the Elderly, 2001
Jack Burks, G. Kim Bigley, Haydon Hill
Medications for fatigue are only partially effective. Amantadine (Symmetrel) is often the first-line treatment. CNS-stimulating drugs such as pemoline (Cylert), methylphenidate (Ritalin), and dexedrine sulfate (Dexedrine) are helpful but are fraught with potential problems. Selective serotoninergic reuptake inhibitors (SSRIs) may also be helpful. More recently, modafinil (Provigil) has been shown to be very effective in the treatment in MS fatigue and has become the first-line treatment for a growing number of physicians.33 Last, 4-aminopyridine is being studied for the treatment of fatigue. However, 4-aminopyridine may precipitate seizures.
Neuromodulation of neurological disorders in a demyelination model: effect of a potassium channel inhibitor from Androctonus scorpion venom
Published in Toxin Reviews, 2023
Hadjila Moussaoui, Amina Ladjel-Mendil, Fatima Laraba-Djebari
The 4-Aminopyridine (4-AP), a potent and non-selective inhibitor of voltage-gated potassium channels, can restore the conduction in demyelinated axons and potentiate synaptic transmission by increasing the release of neurotransmitters in synapses (Jensen et al.2014). The 4-AP (Dalfampridine, Ampyra®), is currently used as a symptomatic treatment of patients with MS. However, 4-AP appears to have unpleasant side effects in some cases of MS patients, which may result from 4-AP blocking a wide array of KV channels involved in different neurophysiological functions in the CNS (Espejo and Montalban 2012, Jensen et al.2014). The fact that 4-AP blocks a wide variety of KV channels make the mechanisms by which it exerts its therapeutic effects so difficult to understand (Jukkola et al.2017).
Current challenges in the pathophysiology, diagnosis, and treatment of paroxysmal movement disorders
Published in Expert Review of Neurotherapeutics, 2021
Cécile Delorme, Camille Giron, David Bendetowicz, Aurélie Méneret, Louise-Laure Mariani, Emmanuel Roze
CACNA1A-related episodic ataxia usually starts in childhood or adolescence [148]. It is typically characterized by attacks of cerebellar ataxia (a few episodes per year to several episodes per week), often associated with nausea and vertigo, lasting from a few hours to a few days. Precipitating factors may include alcohol or coffee intake, stress, and exercise. Patients tend to develop slowly progressive ataxia with nystagmus over the course of the disease. Additional manifestations of the disease may include migraine, epilepsy, dystonia, fluctuating weakness, and intellectual disability. The majority of patients have a good response to acetazolamide [148]. Treatment with 4-aminopyridine could be an interesting alternative [149].
Neuro-Ophthalmic Literature Review
Published in Neuro-Ophthalmology, 2020
David A. Bellows, John J. Chen, Hui-Chen Cheng, Peter W. MacIntosh, Jenny A. Nij Bijvank, Michael S. Vaphiades, Konrad P. Weber, Sui H. Wong
This extensive paper describes combined in vivo and in vitro evidence of the neuroprotective effects of the drug 4-aminopyridine (4-AP) in experimental optic neuritis and multiple sclerosis (MS). 4-AP is approved for the symptomatic treatment of walking disability in MS and has been shown to improve a broad range of other clinical and self-reported outcome measures in MS patients as well. The mode of action and some pre-clinical evidence suggest a more long-standing effect of 4-AP on top of symptomatic effects.