Hits and misses with animal models of narcolepsy and the implications for drug discovery.
Expert Opin Drug Discov
; 19(6): 755-768, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38747534
ABSTRACT
INTRODUCTION:
Narcolepsy is a chronic and rare neurological disorder characterized by disordered sleep. Based on animal models and further research in humans, the dysfunctional orexin system was identified as a contributing factor to the pathophysiology of narcolepsy. Animal models played a larger role in the discovery of some of the pharmacological agents with established benefit/risk profiles. AREAS COVERED In this review, the authors examine the phenotypes observed in animal models of narcolepsy and the characteristics of clinically used pharmacological agents in these animal models. Additionally, the authors compare the effects of clinically used pharmacological agents on the phenotypes in animal models with those observed in narcolepsy patients. EXPERT OPINION Research in canine and mouse models have linked narcolepsy to the O×R2mutation and orexin deficiency, leading to new diagnostic criteria and a drug development focus. Advancements in pharmacological therapies have significantly improved narcolepsy management, with insights from both clinical experience and from animal models having led to new treatments such as low sodium oxybate and solriamfetol. However, challenges persist in addressing symptoms beyond excessive daytime sleepiness and cataplexy, highlighting the need for further research, including the development of diurnal animal models to enhance understanding and treatment options for narcolepsy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Modelos Animales de Enfermedad
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Descubrimiento de Drogas
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Orexinas
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Desarrollo de Medicamentos
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Narcolepsia
Límite:
Animals
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Humans
Idioma:
En
Revista:
Expert Opin Drug Discov
Año:
2024
Tipo del documento:
Article
País de afiliación:
India