pitolisant, a novel histamine-3 receptor competitive antagonist, and inverse agonist, in the treatment of excessive daytime sleepiness in adult patients with narcolepsy

Sarfraz, Noeen; Okuampa, David; Hansen, Hannah; Álvarez, M.; Cornett, Elyse M.; Kakazu, Juyeon; Kaye, Adam M.; Kaye, Alan D.

doi:10.52965/001c.34222

Cited by 10 publications

(6 citation statements)

References 23 publications

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“…Asimismo, modula la actividad de otros neurotransmisores, aumentando los niveles de acetilcolina, noradrenalina y dopamina, sin actuar sobre las neuronas dopaminérgicas del núcleo accumbens , por lo que no presenta riesgo de adicción. De esta manera, al potenciar la actividad histaminérgica, mejora el nivel de alerta, la duración de la vigilia y los episodios de cataplejía [ 7 , 8 ].…”

Section: Discussionunclassified

Narcolepsia multirresistente

González García,

Morán Sánchez,

Sánchez Serrano

et al. 2023

RevNeurol

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Introducción. La narcolepsia de tipo 1 es una enfermedad degenerativa focal del hipotálamo que afecta selectivamente a las neuronas productoras de orexina (hipocretina). Presenta múltiples manifestaciones clínicas, tanto en vigilia como en sueño. Con frecuencia, los síntomas son tan disruptivos que ocasionan enorme sufrimiento y deterioro de la calidad de vida de los pacientes. Aunque en ocasiones es suficiente con un abordaje no farmacológico, la gran mayoría de los enfermos necesita medicación para un adecuado control clínico. Caso clínico. Varón que a los 43 años comenzó a presentar de forma aguda excesiva somnolencia diurna y episodios de cataplejía. Tras un exhaustivo estudio se le diagnosticó narcolepsia de tipo 1. A lo largo de la evolución de la enfermedad se le prescribieron antidepresivos, neuroestimulantes y oxibato sódico, en monoterapia o en combinación. La respuesta al tratamiento farmacológico fue insuficiente y se acompañó de numerosos efectos secundarios. Tras la introducción de pitolisant se objetivó una franca mejoría de los síntomas, y se consiguió reducir la dosis de los otros fármacos y de sus efectos adversos. Conclusión. Son numerosas las medidas disponibles en la actualidad para abordar los síntomas cardinales de la enfermedad, aunque siguen existiendo casos resistentes al tratamiento antinarcoléptico. Los fármacos con mecanismos de acción sobre receptores del sistema histaminérgico pueden resultar de gran utilidad en estos casos.

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Section: Discussionunclassified

Narcolepsia multirresistente

González García,

Morán Sánchez,

Sánchez Serrano

et al. 2023

RevNeurol

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“…Interestingly, histamine also modulates the wake-sleep cycle in higher organisms. For instance, pitolisant (H3R receptor antagonist/inverse agonist) is a narcolepsy treatment option [82,83] and modafinil (a drug increasing histamine release in the neocortex and hypothalamus [84,85]) is a wake-promoting agent to treat hypersomnolence [86,87]. These results certainly encourage further research on the role of histamine in the sleep-wake cycle and circadian rhythm regulation.…”

Section: Wake-sleep Cyclementioning

confidence: 98%

A Closer Look at Histamine in Drosophila

Volonté,

Liguori,

Amadio

2024

IJMS

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The present work intends to provide a closer look at histamine in Drosophila. This choice is motivated firstly because Drosophila has proven over the years to be a very simple, but powerful, model organism abundantly assisting scientists in explaining not only normal functions, but also derangements that occur in higher organisms, not excluding humans. Secondly, because histamine has been demonstrated to be a pleiotropic master molecule in pharmacology and immunology, with increasingly recognized roles also in the nervous system. Indeed, it interacts with various neurotransmitters and controls functions such as learning, memory, circadian rhythm, satiety, energy balance, nociception, and motor circuits, not excluding several pathological conditions. In view of this, our review is focused on the knowledge that the use of Drosophila has added to the already vast histaminergic field. In particular, we have described histamine’s actions on photoreceptors sustaining the visual system and synchronizing circadian rhythms, but also on temperature preference, courtship behavior, and mechanosensory transmission. In addition, we have highlighted the pathophysiological consequences of mutations on genes involved in histamine metabolism and signaling. By promoting critical discussion and further research, our aim is to emphasize and renew the importance of histaminergic research in biomedicine through the exploitation of Drosophila, hopefully extending the scientific debate to the academic, industry, and general public audiences.

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“…Different from traditional stimulants, pitolisant works by enhancing the release of histamine, promoting wakefulness and reducing excessive sleepiness 14 . The robust efficacy of pitolisant for the reduction in both EDS and cataplexy has been demonstrated 15–18 . In addition, pitolisant has been found to be well‐tolerated and has a low risk of abuse.…”

Section: Introductionmentioning

confidence: 99%

“… 14 The robust efficacy of pitolisant for the reduction in both EDS and cataplexy has been demonstrated. 15 , 16 , 17 , 18 In addition, pitolisant has been found to be well‐tolerated and has a low risk of abuse. Recent real‐world studies have suggested that pitolisant treatment is effective in children with narcolepsy and also is well tolerated.…”

Section: Introductionmentioning

confidence: 99%

Is pitolisant safe for clinical use? A retrospective pharmacovigilance study focus on the post‐marketing safety

Jiang,

Qian,

Jiang

et al. 2024

Pharmacology Res & Perspec

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Pitolisant, a novel histamine H3‐receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real‐world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant‐associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant‐associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life‐threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.

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pitolisant, a novel histamine-3 receptor competitive antagonist, and inverse agonist, in the treatment of excessive daytime sleepiness in adult patients with narcolepsy

Cited by 10 publications

References 23 publications

Narcolepsia multirresistente

Narcolepsia multirresistente

A Closer Look at Histamine in Drosophila

Is pitolisant safe for clinical use? A retrospective pharmacovigilance study focus on the post‐marketing safety

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