{{Short description|Hypnotic sedative drug}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 461936069 | IUPAC_name = ''N''-methyl-''N''-[3-[3-(thiophene-2-carbonyl)<br>pyrazolo[5,1-b]pyrimidin-7-yl]phenyl]acetamide | image = Indiplon.svg | image_class = skin-invert-image | width = 175px <!--Clinical data-->| tradename = | pregnancy_US = | legal_US = | routes_of_administration = Oral <!--Pharmacokinetic data-->| bioavailability = | metabolism = | elimination_half-life = 1.5–1.8 hours | excretion = <!--Identifiers--> | IUPHAR_ligand = 4221 | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 325715-02-4 | ATC_prefix = none | ATC_suffix = | PubChem = 6450813 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4953363 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 8BT63DA42E | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D02640 | ChEBI = 188583 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 262075 <!--Chemical data-->| C = 20 | H = 16 | N = 4 | O = 2 | S = 1 | smiles = O=C(C1=CC=CS1)C2=C3N=CC=C(C4=CC(N(C)C(C)=O)=CC=C4)N3N=C2 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C20H16N4O2S/c1-13(25)23(2)15-6-3-5-14(11-15)17-8-9-21-20-16(12-22-24(17)20)19(26)18-7-4-10-27-18/h3-12H,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = CBIAWPMZSFFRGN-UHFFFAOYSA-N }}

'''Indiplon''' (INN and USAN) is an unmarketed nonbenzodiazepine, hypnotic sedative 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, like most other nonbenzodiazepine sedatives. It primarily binds to benzodiazepine sites on α<sub>1</sub> subunit-containing GABA<sub>A</sub> receptors in the brain.<ref>{{cite journal | vauthors = Petroski RE, Pomeroy JE, Das R, Bowman H, Yang W, Chen AP, Foster AC | title = Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 1 | pages = 369–77 | date = April 2006 | pmid = 16399882 | doi = 10.1124/jpet.105.096701 | s2cid = 46510829 | url = http://jpet.aspetjournals.org/cgi/content/full/317/1/369 | format = PDF | url-access = subscription }}</ref>

=== Pharmacokinetics === Indiplon has a short elimination half-life of 1.5 to 1.8 hours in young and elderly subjects, respectively.<ref>{{cite journal | vauthors = Lemon MD, Strain JD, Hegg AM, Farver DK | title = Indiplon in the management of insomnia | journal = Drug Design, Development and Therapy | volume = 3 | pages = 131–142 | date = September 2009 | pmid = 19920929 | pmc = 2769245 | doi = 10.2147/dddt.s3207 | doi-access = free }}</ref>

== Chemistry == Indiplon is a pyrazolopyrimidine related to the nonbenzodiazepine hypnotic zaleplon.<ref>{{cite journal | vauthors = Sullivan SK, Petroski RE, Verge G, Gross RS, Foster AC, Grigoriadis DE | title = Characterization of the interaction of indiplon, a novel pyrazolopyrimidine sedative-hypnotic, with the GABAA receptor | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 311 | issue = 2 | pages = 537–546 | date = November 2004 | pmid = 15256540 | doi = 10.1124/jpet.104.071282 }}</ref>

==History== Indiplon was discovered at Lederle Laboratories (which was later acquired by Wyeth) in the 1980s and was called CL 285,489.<ref name=Neubauer>{{cite book | vauthors = Neubauer DN | chapter = Indiplon | pages = 453–464 | title = GABA and Sleep: Molecular, Functional and Clinical Aspects. | veditors = Monti JS, Pandi-Perumal SR, Möhler H | publisher = Springer Science & Business Media | date = 2010 | isbn = 9783034602266 }}</ref>{{rp|454}} 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.<ref name=Neubauer/> In 2002, Neurocrine entered into an agreement with Pfizer to develop the drug.<ref name=Neubauer/>

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.<ref>{{cite web | url = http://www.fool.com/investing/general/2010/06/18/san-diegos-neurocrine-biosciences-scores-second-bi.aspx | title = San Diego's Neurocrine Biosciences Scores Second Big Deal in Two Days | work = The Motley Fool | date = 18 June 2010 }}</ref> However, following the issuing of a non-approvable letter for the modified-release 15&nbsp;mg formulation and an approvable letter with stipulations for the 5&nbsp;mg and 10&nbsp;mg immediate-release version by the FDA in May 2006,<ref>{{cite web | url = http://www.thestreet.com/story/10285854/2/neurocrines-fda-nightmare.html | title = Neurocrine's FDA Nightmare | work = TheStreet.com | date = 16 May 2006 }}</ref> Pfizer ended its relationship with Neurocrine.<ref>{{cite web | url = http://www.thestreet.com/story/10293335/pfizer-drops-neurocrine-deal.html | title = Pfizer Drops Neurocrine Deal | work = TheStreet.com | date = 22 June 2006 }}</ref> Neurocrine's stock price dropped 60% on the news.<ref>{{cite web | url = https://money.cnn.com/2006/05/16/news/companies/indiplon/index.htm | archive-url = https://web.archive.org/web/20160304101515/http://money.cnn.com/2006/05/16/news/companies/indiplon/index.htm | url-status = dead | archive-date = March 4, 2016 | title = Neurocrine stock price plunges 60 percent:FDA's mixed review of sleeping pill Indiplon could threaten Pfizer-Neurocrine partnership | work = CNN Money | date = 15 May 2006 }}</ref>

Following a resubmission, the FDA in December 2007 deemed Neurocrine's new drug application (NDA) 'approvable' in the 5 and 10&nbsp;mg formulations,<ref name="pr1213">{{cite press release | title = Neurocrine Receives Approvable Letter for Indiplon Capsules with Additional Safety and Efficacy Data Required by FDA | publisher = Neurocrine Biosciences, Inc. | date = 2007-12-13 | url = https://www.drugs.com/nda/indiplon_071213.html | access-date = 2007-12-13 }}</ref> 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.<ref name="pressrelease1">{{Cite web |title=Additional Pipeline Projects |url=http://www.neurocrine.com/index.cfm?navId=25 |publisher=Neurocrine |date=2012-02-16 |archive-url=https://web.archive.org/web/20120327204702/http://www.neurocrine.com/index.cfm?navId=25 |archive-date=2012-03-27 |url-status=live |access-date=2014-06-24 }}</ref>

Following the 2007 FDA letter, Neurocrine decided to discontinue all clinical and marketing development of Indiplon in the United States.<ref name="pr1213" /><ref name="pressrelease1" />

== References == {{reflist}}

== External links == * [https://www.drugs.com/NDA/indiplon_041019.html 2004 press release announcing Neurocrine's new product, Indiplon] * [http://www.genome.jp/dbget-bin/www_bget?dr+D02640 GenomeNet Entry: D02640]

{{Hypnotics and sedatives}} {{GABAAR PAMs}}

Category:Hypnotics Category:Pyrazolopyrimidines Category:Sedatives Category:Diarylketones Category:Thiophenes Category:Acetanilides Category:GABAA receptor positive allosteric modulators