Indiplon

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Indiplon
Indiplon.svg
Systematic (IUPAC) name
N-methyl-N-[3-[3-(thiophene-2-carbonyl)
pyrazolo[5,1-b]pyrimidin-7-yl]phenyl]acetamide
Clinical data
Legal status
Routes

Oral

C
Identifiers
CAS number 325715-02-4 N
ATC code None
PubChem CID 6450813
ChemSpider 4953363 N
UNII 8BT63DA42E N
KEGG D02640 N
ChEMBL CHEMBL262075 N
Chemical data
Formula C20H16N4O2S 
Mol. mass 376.0993
 N (what is this?)  (verify)

Indiplon (INN and USAN) is a nonbenzodiazepine, hypnotic sedative that was developed in 2 formulations - an immediate release product for sleep onset and a modified-release (a.k.a. controlled-release or extended-release) version for sleep maintenance.

Mode of action[edit]

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 GABAA receptors in the brain.[1]

Availability[edit]

Indiplon was originally scheduled for release in 2007, when Sanofi-Aventis' popular hypnotic zolpidem 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 to co-market indiplon in the US, in a deal worth a potential $400mn.[2] 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,[3] Pfizer ended its relationship with Neurocrine.[4] Neurocrine's stock price dropped 60% on the news.[5]

Following a resubmission, the FDA in December 2007 deemed Neurocrine's new drug application (NDA) 'approvable' in the 5 and 10 mg formulations,[6] 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.[7]

Following the 2007 FDA letter, Neurocrine decided to discontinue all clinical and marketing development of Indiplon in the United States.[6][7]

References[edit]

  1. ^ Petroski RE, Pomeroy JE, Das R et al. (April 2006). "Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors" (PDF). J. Pharmacol. Exp. Ther. 317 (1): 369–77. doi:10.1124/jpet.105.096701. PMID 16399882. 
  2. ^ San Diego's Neurocrine Biosciences Scores Second Big Deal in Two Days - The Motley Fool, 18 June 2010
  3. ^ Neurocrine's FDA Nightmare - TheStreet.com, 16 May 2006
  4. ^ Pfizer Drops Neurocrine Deal - TheStreet.com, 22 June 2006
  5. ^ Neurocrine stock price plunges 60 percent:FDA's mixed review of sleeping pill Indiplon could threaten Pfizer-Neurocrine partnership - CNN Money, 15 May 2006
  6. ^ a b "Neurocrine Receives Approvable Letter for Indiplon Capsules with Additional Safety and Efficacy Data Required by FDA" (Press release). Neurocrine Biosciences, Inc. 2007-12-13. Retrieved 2007-12-13. 
  7. ^ a b "Additional Pipeline Projects". Neurocrine. 2012-02-16. Archived from the original on 2012-02-20. Retrieved 2014-06-24. 

External links[edit]