Indiplon (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

and

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...

) is a

nonbenzodiazepine Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive drugs that are very benzodiazepine-like in nature. They are used in the treatment of sleep proble ...

hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

that was developed in two formulations—an immediate-release formulation for sleep onset, and a modified-release (also called controlled-release or extended-release) version for sleep maintenance.

Mode of action

Indiplon works by enhancing the action of the inhibitory neurotransmitter GABA, like most other nonbenzodiazepine sedatives. It primarily binds to the α₁ subunits of the GABA_A receptors in the brain.

History

Indiplon was discovered at

Lederle Laboratories American Cyanamid Company was a leading American conglomerate which became one of the nation's top 100 manufacturing companies during the 1970s and 1980s, according to the Fortune 500 listings at the time. It started in fertilizer, but added m ...

(which was later acquired by

Wyeth Wyeth, LLC was an American pharmaceutical company. The company was founded in Philadelphia, Pennsylvania, in 1860 as ''John Wyeth and Brother''. It was later known, in the early 1930s, as American Home Products, before being renamed to Wyeth in ...

) in the 1980s and was called CL 285,489. In 1998 Lederle licensed it, along with other early stage drug candidates, to

DOV Pharmaceutical DOV Pharmaceutical was a biotechnology company that focused on therapies primarily for central nervous system conditions. It was founded in 1995 by former employees of American Cyanamid (which was acquired by Wyeth in 1994), and in 1998 it in-lic ...

, a startup formed by former Lederle employees, and Dov exclusively sublicensed its rights in the drug to

Neurocrine Biosciences Neurocrine Biosciences, Inc. is an American biopharmaceutical company founded in 1992. The company is headquartered in San Diego, California, and led by CEO Kevin Gorman. Neurocrine develops treatments for neurological and endocrine-related diseas ...

in that same year. In 2002, Neurocrine entered into an agreement with Pfizer to develop the drug. Indiplon was originally scheduled for release in 2007, when

Sanofi-Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

' popular hypnotic

zolpidem Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behaviora ...

lost its patent rights in the United States and thus became available as a much less expensive generic. In 2002,

had entered into an agreement with

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

to co-market indiplon in the US, in a deal worth a potential $400mn. However, following the issuing of a non-approvable letter for the modified-release 15 mg formulation and an

approvable letter Approvable letters, and the related non-approvable letters (alternately not-approvable letters), were notifications sent out by the Food and Drug Administration (FDA) to drug manufacturers alerting them to the approval prospects of their drugs unde ...

with stipulations for the 5 mg and 10 mg immediate-release version by the FDA in May 2006,

ended its relationship with Neurocrine. Neurocrine's stock price dropped 60% on the news. Following a resubmission, the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

in December 2007 deemed Neurocrine's new drug application (NDA) 'approvable' in the 5 and 10 mg formulations, but requested new studies as a prerequisite to approval, including a clinical trial in the elderly, a safety study comparing adverse effects to those of similarly marketed drugs, and a preclinical study examining indiplon's safety in the third trimester of pregnancy. Following the 2007 FDA letter, Neurocrine decided to discontinue all clinical and marketing development of Indiplon in the United States.

References

External links

Neurocrine's drug pipeline page referencing indiplon

* ttp://www.pfizer.com/ Pfizer
GenomeNet Entry: D02640
{{GABAAR PAMs Hypnotics Pyrazolopyrimidines Sedatives Ketones Thiophenes Acetanilides GABAA receptor positive allosteric modulators