The Stanford University Sleep Disorders Center has established a colony of dogs affected with a genetically transmitted form of narcolepsy. We now propose extensive in vivo and in vitro pharmacological investigations utilizing this animal model in order to further understand the neurotransmitter defects in narcolepsy and to elaborate new therapeutic strategies for human narcolepsy.
The specific aims of this project are: * To study the effects of monoaminergic and muscarinic agonists and antagonists selective for receptor subtypes on canine cataplexy. * To study the binding properties of these agents in vitro and to correlate these properties with in vivo effects on canine cataplexy. * To study the influence of nighttime sleep on daytime canine cataplexy. Nighttime sleep will be manipulated by various alerting and hypnogenic drugs (especially those increasing REM sleep). A key variable will be the intensity of cataplexy on the following day. * To study the effect of prazosin (an alpha 1 antagonist) and yohimbine (an alpha 2 antagonist) on human narcoleptic patients.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurology C Study Section (NEUC)
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Stanford University
Schools of Medicine
United States
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