Indiplon ( INN and USAN) is a unmarketed

nonbenzodiazepine Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive, depressant, sedative, hypnotic, anxiolytic drugs that are benzodiazepine-like in uses, such as f ...

hypnotic A hypnotic (from Ancient Greek, Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to sleep induction, induce sleep and to trea ...

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

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.

Pharmacology

Pharmacodynamics

Indiplon works by enhancing the action of the inhibitory neurotransmitter

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

, like most other nonbenzodiazepine sedatives. It primarily binds to the α₁ subunits of the GABA_A receptors in the brain.

Pharmacokinetics

Indiplon has a short elimination half-life of 1.5 to 1.8 hours in young and elderly subjects, respectively.

Chemistry

Indiplon is a pyrazolopyramidine related to the nonbenzodiazepine hypnotic

zaleplon Zaleplon, sold under the brand name Sonata among others, is a sedative and hypnotic which is used to treat insomnia. It is a nonbenzodiazepine or Z-drug of the pyrazolopyrimidine class. It was developed by King Pharmaceuticals and approved fo ...

History

Indiplon was discovered at Lederle Laboratories (which was later acquired by

Wyeth Wyeth Pharmaceuticals Inc. was a pharmaceutical company until it was purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania, in 1860 as John Wyeth and Brother. Its headquarters moved to Collegeville, Pennsylvania, a ...

) in the 1980s and was called CL 285,489. In 1998 Lederle licensed it, along with other early stage drug candidates, to DOV Pharmaceutical, a startup formed by former Lederle employees, and Dov exclusively sublicensed its rights in the drug to Neurocrine Biosciences 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. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Synthélabo merg ...

' 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 after beh ...

lost its patent rights in the United States and thus became available as a much less expensive generic. In 2002, Neurocrine Biosciences had entered into an agreement with

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

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 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 The Food and Drug Administration's (FDA) New Drug Application (NDA) is the vehicle in the United States through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing. Some 30% or less of initial ...

(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

2004 press release announcing Neurocrine's new product, Indiplon

GenomeNet Entry: D02640
{{GABAAR PAMs Hypnotics Pyrazolopyrimidines Sedatives Diarylketones Thiophenes Acetanilides GABAA receptor positive allosteric modulators