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Mechanism of action of narcolepsy medications

Published online by Cambridge University Press:  18 November 2014

Chandan R. Gowda  and
Leslie P. Lundt
Chandan R. Gowda*
Affiliation:
Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona, USA
Leslie P. Lundt
Affiliation:
Santa Barbara County Alcohol, Drug and Mental Health Services, Psychiatric Health Facility, Santa Barbara, CA, USA
*
*Address for correspondence: Chandan Gowda, Midwestern University, 19555N 59th Avenue, Glendale, AZ 85308, USA. (Email: [email protected])
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Abstract

The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective.

Keywords

Cataplexyhypersomniahypocretinnarcolepsyorexinsleep
Type
CME Review Article
Information
CNS Spectrums , Volume 19 , Issue S1: CME SUPPLEMENT , December 2014 , pp. 25 - 34
Copyright
© Cambridge University Press 2014 

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Footnotes

This activity is supported by an educational grant from Jazz Pharmaceuticals, Inc.

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