F-15063
{{Chembox
| ImageFile = F 15 063.svg
| ImageSize =
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| PIN = N-{[3-(Cyclopent-1-en-1-yl)phenyl]methyl}-2-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]ethan-1-amine
| OtherNames = F-15,063
|Section1={{Chembox Identifiers
| CASNo = 680203-70-7
| UNII = 115OSL8W3F
| PubChem = 10248159
| ChEMBL = 218261
| ChemSpiderID = 8423646
| StdInChI=1S/C24H29NO2/c1-24(2)16-21-11-6-12-22(23(21)27-24)26-14-13-25-17-18-7-5-10-20(15-18)19-8-3-4-9-19/h5-8,10-12,15,25H,3-4,9,13-14,16-17H2,1-2H3
| StdInChIKey = RAIDOKRWKAIHOH-UHFFFAOYSA-N
| SMILES = CC1(CC2=C(O1)C(=CC=C2)OCCNCC3=CC=CC(=C3)C4=CCCC4)C
}}
|Section2={{Chembox Properties
| Formula = C24H29NO2
| MolarMass = 363.49 g mol−1
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|Section3={{Chembox Hazards
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F-15,063 is an orally active potential antipsychotic, and an antagonist at the D2/D3 receptors, partial agonist at the D4 receptor, and agonist at the 5-HT1A receptors. It has greater efficacy at the 5-HT1A receptors than other antipsychotics, such as clozapine, aripiprazole, and ziprasidone. This greater efficacy may lead to enhanced antipsychotic properties, as antipsychotics that lack 5-HT1A affinity are associated with increased risk of extrapyramidal symptoms, and lack of activity against the negative symptoms of schizophrenia.{{cite journal|last=Newman-Tancredi|first=A.|title=F15063, a potential antipsychotic with D2/D3 antagonist, 5-HT1A agonist and D4 partial agonist properties: (I) in vitro receptor affinity and efficacy profile|journal=British Journal of Pharmacology|date=May 2007|volume=151|issue=2|pages=237–52|pmid=17375087|doi=10.1038/sj.bjp.0707158|pmc=2013955}}
As expression of immediate-early gene (IEG) in certain brain regions may represent markers of anti-psychotic activity, expression of immediate-early gene mRNA in the prefrontal cortex and striatum was measured. Treatment with F-15,063 resulted in induction of c-fos and fosB mRNA expression in the prefrontal cortex. In the striatum, F-15,063 treatment resulted in induction of all
IEGs studied (c-fos, fosB, zif268, c-jun, junB, nor1, nur77, arc).{{cite journal|last=Bruins Slot|first=LA|title=F15063, a potential antipsychotic with dopamine D(2)/D(3) receptor antagonist and 5-HT(1A) receptor agonist properties: influence on immediate-early gene expression in rat prefrontal cortex and striatum.|journal=European Journal of Pharmacology|date=October 2009|volume=620|issue=1–3|pages=27–35|doi=10.1016/j.ejphar.2009.08.019|pmid=19695244}}
F-15,063 was tested in several animal models that predict antipsychotic activity to help determine the behavioral profile. Administration of F-15,063 blocked amphetamine and ketamine induced hyperlocomotion, but did not affect baseline, spontaneous locomotor activity. In addition, F-15,063 did not produce catalepsy, a side effect of other antipsychotics, such as haloperidol. This inhibition of catalepsy is 5-HT1A receptor mediated, as pretreatment with the 5-HT1A antagonist WAY-100635 reinstated catalepsy. The level of catalepsy did not increase with chronic dosing, and there was no evidence for serotonin syndrome at clinically relevant doses.{{cite journal|last=Depoortère|first=R.|title=F15063, a compound with D2/D3 antagonist, 5-HT 1A agonist and D4 partial agonist properties. II. Activity in models of positive symptoms of schizophrenia|journal=British Journal of Pharmacology|date=May 2007|volume=151|issue=2|pages=253–65|doi=10.1038/sj.bjp.0707159|pmid=17375086|pmc=2013947}}
Plasma levels of F-15,063 decreased seven-fold 4 hours after oral administration, and 25-fold after 8 hours. Despite this, there was still a high (65%) level of central D2 occupancy at 4 hours, and it retained its full antipsychotic potential at this time point. Even after 8 hours, F-15,063 still demonstrated some central D2 occupancy, and retained some antipsychotic activity.{{cite journal|last=Assié|first=MB|title=F15063, a potential antipsychotic with dopamine D(2)/D(3) antagonist, 5-HT(1A) agonist and D(4) partial agonist properties: (IV) duration of brain D2-like receptor occupancy and antipsychotic-like activity versus plasma concentration in mice|journal=Naunyn-Schmiedeberg's Archives of Pharmacology|date=June 2007|volume=375|issue=4|pages=241–50|doi=10.1007/s00210-007-0162-x|pmid=17453175|s2cid=20594732 }}