0058 Scientific Rationale and Clinical Development of AXS-12 for Narcolepsy.

[摘要] IntroductionNarcolepsy is a serious neurological condition causing sleep-wake dysregulation and is characterized by excessive daytime sleepiness (EDS) and cataplexy. Cataplexy is seen in approximately 70% of patients and is a sudden reduction or loss of muscle tone while a patient is awake. Narcolepsy interferes with cognitive, psychological, and social functioning, increases the risk of accidents, and is associated with greater mortality. Depression is reported in up to 57% of patients. Currently-approved treatments are few for this under-diagnosed orphan condition, and are limited by variability in efficacy, tolerability issues and the need for scheduling. AXS-12 (reboxetine) is a highly selective and potent inhibitor of norepinephrine reuptake. The scientific rationale for developing AXS-12 for the treatment of narcolepsy is based on in vivo nonclinical physiological and pharmacological studies suggesting a strong role for adrenergic neurotransmission in cataplexy, anti-cataplectic effects of reboxetine in orexin-deficient mice, and positive preliminary clinical evidence from an open-label pilot study of reboxetine in patients with narcolepsy.

[学科分类] 生理学