Piromelatine (also known as Neu-P11) is an investigational therapy being developed by Neurim Pharmaceuticals to help manage sleeping difficulties. The compound is now being studied for its potential to improve cognitive function and slow the progression of Alzheimer’s disease by promoting better sleep.

How Piromelatine works

Sleeping, wakefulness, metabolism, and body temperature are regulated through a daily cycle known as the circadian rhythm, also referred to as the “body clock.” Melatonin is a chemical that plays a key role in inducing sleep and synchronizing the sleep-wake cycle. Melatonin also is involved in learning and memory.

Many Alzheimer’s disease patients have a disrupted circadian rhythm, causing them to experience a variety of sleeping problems, such as sleeping longer than usual and waking up frequently throughout the night. Interrupted sleep also may lead to a buildup of toxins harmful to the brain, worsening disease symptoms.

Piromelatine is an oral treatment that improves sleep by modifying different chemical systems in the brain. For example, by stimulating melatonin receptors 1 (MT1) and 2 (MT2), Piromelatine can promote sleep. It also can improve memory, enhance mood, and reduce nighttime wakefulness by stimulating the serotonin receptor 5-HT1A. Its combined activity on both melatonin and serotonin receptors may help stimulate nerve cell growth in the brain.

Piromelatine in clinical trials

In a rat model of Alzheimer’s disease, a single injection of Piromelatine into the brain improved cognitive functions and memory, and provided protection against nerve cell death. A mouse study also supports the effectiveness of Piromelatine in treating sleep disturbances.

In 2015, Neurim launched the ReCOGNITION study, a Phase 2 clinical trial (NCT02615002) to determine a Piromelatine dose that can effectively improve cognitive performance, as well as its safety and tolerability in patients with mild Alzheimer’s disease.

The study enrolled 500 patients who were given a daily dose of either 5 mg, 20 mg, or 50 mg of Piromelatine or placebo for six months. Assessments are being made regarding patients’ change of cognitive function and ability to perform normal daily activities. The study is active and completion is estimated for November 2019. 

Additional information

Piromelatine is classified as a new chemical entity by the U.S. Food and Drug Administration (FDA), a designation given to compounds that contain active components not found in other FDA-approved drugs.

Piromelatine has been tested in Phase 1 (NCT01114126) and Phase 2 (NCT01489969) clinical trials in patients with primary insomnia (difficulty sleeping). The treatment was able to induce deeper sleep with fewer awakenings, and was safe and well-tolerated, with no effects on mental performance the next day.

Piromelatine also was evaluated in a Phase 2 clinical trial (NCT01558284) in patients with diarrhea-predominant irritable bowel syndrome.

Other studies in mice have shown that by treating chronic sleep deprivation, Piromelatine may improve impaired metabolic profiles and the body’s response to insulin (a hormone that controls blood sugar levels), reducing the risk of conditions such as type 2 diabeteshigh blood pressure, and obesity.


Last updated: Sept. 10, 2019


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