Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic

Sleep is a basic human function that occupies approximately one-third of our lives. Much of
what is known about the benefits of sleep in humans has been obtained from studies of
patients with insomnia, the most common sleep disorder with a reported prevalence of 10 to
15%. Unfortunately, insomnia is an independent risk factor for acute myocardial infarction,
coronary heart disease, heart failure, hypertension, diabetes, and death. More so, sleep
disturbances lead to neurocognitive deficits such as delirium and psychosis. However, the
principal medications (i.e. benzodiazepines, zolpidem) currently used to treat insomnia are
associated with side effects such as daytime sedation, delirium, anterograde memory
disturbance, and complex sleep-related behaviors. We recently found that a nighttime
intravenous bolus administration of dexmedetomidine was associated with normal sleep
architecture comprising of rapid eye movement (REM) and non-REM (N1, N2, N3) sleep, with
improved next-day psychomotor vigilance performance compared to zolpidem. Presently,
dexmedetomidine is only available in an intravenous formulation. The goal of this project is
to develop dexmedetomidine, an alpha-2 receptor agonist, into an oral sleep therapeutic with
a neurocognitive sparing profile.

Inclusion Criteria:

- Age between 18-50

- Native English speaking

- ASA physical status classification P1 and P2 (stable chronic condition)

- Normal body habitus.

Exclusion Criteria:

- Abnormal sleep habits

- Sleeping less than 5 hours each night

- Going to sleep before 9:00 PM or after 2:00 AM on a regular basis

- Waking up before 5:00 AM or after 10:00 AM on a regular basis.

- Takes medication that alters sleep, cognitive function, or both. -Has a history of a
known neurological or psychiatric problem.

- Younger than 18 or older than 50 years of age.

- Known or suspected sleep disorder(s).