4-aminopyridine – the new old drug for the treatment of neurodegenerative diseases

Kostadinova, Ivanka; Danchev, Nikolai

doi:10.3897/pharmacia.66.e35976

Cited by 17 publications

(8 citation statements)

References 39 publications

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“…In any case, the system administration of CBX is inadequate for studying the effects on the targets in the central nervous system. 4-Aminopyridine (4-AP) is used intravenously and orally to relieve symptoms of Eaton–Lambert syndrome, multiple sclerosis, Huntington’s chorea, Alzheimer’s disease, and some other neurological disorders [ 44 ]. However, to obtain focal epileptic seizures, an adequate dose of 4-AP must be injected locally into the brain tissue [ 45 , 46 ].…”

Section: Methodsmentioning

confidence: 99%

The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

Volnova

Tsytsarev

Ganina³

et al. 2022

IJMS

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Gap junctions (GJs) are intercellular junctions that allow the direct transfer of ions and small molecules between neighboring cells, and GJs between astrocytes play an important role in the development of various pathologies of the brain, including regulation of the pathological neuronal synchronization underlying epileptic seizures. Recently, we found that a pathological change is observed in astrocytes during the ictal and interictal phases of 4-aminopyridin (4-AP)-elicited epileptic activity in vitro, which was correlated with neuronal synchronization and extracellular epileptic electrical activity. This finding raises the question: Does this signal depend on GJs between astrocytes? In this study we investigated the effect of the GJ blocker, carbenoxolone (CBX), on epileptic activity in vitro and in vivo. Based on the results obtained, we came to the conclusion that the astrocytic syncytium formed by GJ-associated astrocytes, which is responsible for the regulation of potassium, affects the formation of epileptic activity in astrocytes in vitro and epileptic seizure onset. This effect is probably an important, but not the only, mechanism by which CBX suppresses epileptic activity. It is likely that the mechanisms of selective inhibition of GJs between astrocytes will show important translational benefits in anti-epileptic therapies.

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Section: Methodsmentioning

confidence: 99%

The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

Volnova

Tsytsarev

Ganina³

et al. 2022

IJMS

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“…4-AP functions as a potassium K + channel blocker, and it is clinically approved to treat walking deficiencies in patients with MS. It helps to improve nerve conduction induced by demyelination [ 137 ]. It is commercialized under the trade name of Ampyra (dalfampridine) and is available as 10 mg tablets.…”

Section: On Treatment Metabolically and Biochemically-derived Preclin...mentioning

confidence: 99%

Hydrogen Ion Dynamics as the Fundamental Link between Neurodegenerative Diseases and Cancer: Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis on Multiple Sclerosis

Harguindey¹,

Alfarouk

Orozco³

et al. 2022

IJMS

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The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally assessed for the first time in order to integrate neurodegeneration within the energetics of the cancer acid–base conceptual frame. At all levels of study (molecular, biochemical, metabolic, and clinical), the intimate nature of both processes appears to consist of opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranging original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows us to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) is an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Furthermore, within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth. Finally, and for the first time, a new and integrated model of treatment for MS can now be advanced.

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“…4-AP works as a potassium K⁺ channel blocker and it is clinically approved to treat walking deficiencies in patients with MS. It helps to improve nerve conduction induced by demyelination [132]. It is commercialized under the trade name of Ampyra (dalfampridine) and is available as 10 mg tablets.…”

Section: Aminopyridine (4-ap)mentioning

confidence: 99%

Hydrogen Ion Dynamics as the Fundamental Link Between Neurodegenerative Diseases and Cancer. Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis in Multiple Sclerosis

Harguindey¹,

Alfarouk²,

Orozco³

et al. 2022

Preprint

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The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

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4-aminopyridine – the new old drug for the treatment of neurodegenerative diseases

Cited by 17 publications

References 39 publications

The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

Hydrogen Ion Dynamics as the Fundamental Link between Neurodegenerative Diseases and Cancer: Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis on Multiple Sclerosis

Hydrogen Ion Dynamics as the Fundamental Link Between Neurodegenerative Diseases and Cancer. Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis in Multiple Sclerosis

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