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'''Flesinoxan''' ('''DU-29,373''') is a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[partial agonist|partial]]/near-[[full agonist|full]] [[receptor agonist|agonist]] of the [[phenylpiperazine]] class.<ref name="pmid3207999">{{cite journal | author = Schoeffter P, Hoyer D. | title = Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus. | journal = Br J Pharmacol. | volume = 95 | issue = 3 | pages = 975–985 | year = 1988 | pmid = 3207999 | pmc = 1854240 }}</ref><ref name="Pitchot W, Wauthy J, Legros JJ, Ansseau M 2004 151–5">{{cite journal | pmid = 15013031 | doi=10.1016/S0924-977X(03)00108-1 | volume=14 | issue=2 | year=2004 | month=March | pages=151–5 | author=Pitchot W, Wauthy J, Legros JJ, Ansseau M}}</ref><ref name="pmid8570029">{{cite journal | author = Hadrava V, Blier P, Dennis T, Ortemann C, de Montigny C | title = Characterization of 5-hydroxytryptamine1A properties of flesinoxan: in vivo electrophysiology and hypothermia study | journal = Neuropharmacology | volume = 34 | issue = 10 | pages = 1311–26 | year = 1995 | month = October | pmid = 8570029 | doi = 10.1016/0028-3908(95)00098-Q| url = http://linkinghub.elsevier.com/retrieve/pii/002839089500098Q}}</ref> Originally developed as an [[antihypertensive|antihypertensive agent]],<ref name="pmid3207999"/><ref name="Pitchot W, Wauthy J, Legros JJ, Ansseau M 2004 151–5"/><ref name="pmid2842163">{{cite journal | author = Wouters W, Tulp MT, Bevan P | title = Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors | journal = European Journal of Pharmacology | volume = 149 | issue = 3 | pages = 213–23 | year = 1988 | month = May | pmid = 2842163 | doi = 10.1016/0014-2999(88)90651-6| url = }}</ref> it was later found to possess [[antidepressant]] and [[anxiolytic]] effects in animals.<ref name="pmid1351303">{{cite journal | author = van Hest A, van Drimmelen M, Olivier B | title = Flesinoxan shows antidepressant activity in a DRL 72-s screen | journal = Psychopharmacology | volume = 107 | issue = 4 | pages = 474–9 | year = 1992 | pmid = 1351303 | doi = 10.1007/BF02245258| url = }}</ref><ref name="pmid7972301">{{cite journal | author = Rodgers RJ, Cole JC, Davies A | title = Antianxiety and behavioral suppressant actions of the novel 5-HT1A receptor agonist, flesinoxan | journal = Pharmacology, Biochemistry, and Behavior | volume = 48 | issue = 4 | pages = 959–63 | year = 1994 | month = August | pmid = 7972301 | doi = 10.1016/0091-3057(94)90205-4| url = http://linkinghub.elsevier.com/retrieve/pii/0091-3057(94)90205-4}}</ref> As a result, it was investigated in [[human]] [[clinical trial]]s for the treatment of [[major depressive disorder]] and [[generalized anxiety disorder]] and was found to have robust [[efficacy]] with very high [[tolerability]],<ref name="pmid8263314">{{cite journal | author = Grof P, Joffe R, Kennedy S, Persad E, Syrotiuk J, Bradford D | title = An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression | journal = International Clinical Psychopharmacology | volume = 8 | issue = 3 | pages = 167–72 | year = 1993 | pmid = 8263314 | doi = 10.1097/00004850-199300830-00005| url = }}</ref><ref name="Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart 2004 279–283">{{cite journal | author = Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart | title = Pilot study of flesinoxan, a 5-HT1A agonist, in major depression: Effects on sleep REM latency and body temperature. | journal = Human Psychopharmacology: Clinical and Experimental | volume = 8 | issue = 4 | pages = 279–283 | year = 2004 | url = http://www3.interscience.wiley.com/journal/109710934/abstract | doi = 10.1002/hup.470080407 }}</ref> but for unclear reasons development was halted and it was never marketed. In patients it enhances [[Rapid eye movement sleep|REM]] [[sleep]] latency, decreases [[body temperature]], and increases [[adrenocorticotropic hormone|ACTH]], [[cortisol]], [[prolactin]], and [[growth hormone]] [[Cellular secretion|secretion]].<ref name="Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart 2004 279–283"/><ref name="pmid15013031">{{cite journal | author = Pitchot W, Wauthy J, Legros JJ, Ansseau M | title = Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study | journal = European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology | volume = 14 | issue = 2 | pages = 151–5 | year = 2004 | month = March | pmid = 15013031 | doi = 10.1016/S0924-977X(03)00108-1 | url = }}</ref>
'''Flesinoxan''' ('''DU-29,373''') is a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[partial agonist|partial]]/near-[[full agonist|full]] [[receptor agonist|agonist]] of the [[phenylpiperazine]] class.<ref name="pmid3207999">{{cite journal | author = Schoeffter P, Hoyer D. | title = Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus. | journal = Br J Pharmacol. | volume = 95 | issue = 3 | pages = 975–985 | year = 1988 | pmid = 3207999 | pmc = 1854240 }}</ref><ref name="Pitchot W, Wauthy J, Legros JJ, Ansseau M 2004 151–5">{{cite journal | pmid = 15013031 | doi=10.1016/S0924-977X(03)00108-1 | volume=14 | issue=2 | journal = European Neuropsychopharmacology | year=2004 | title = Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study | month=March | pages=151–5 | author=Pitchot W, Wauthy J, Legros JJ, Ansseau M}}</ref><ref name="pmid8570029">{{cite journal | author = Hadrava V, Blier P, Dennis T, Ortemann C, de Montigny C | title = Characterization of 5-hydroxytryptamine1A properties of flesinoxan: in vivo electrophysiology and hypothermia study | journal = Neuropharmacology | volume = 34 | issue = 10 | pages = 1311–26 | year = 1995 | month = October | pmid = 8570029 | doi = 10.1016/0028-3908(95)00098-Q| url = http://linkinghub.elsevier.com/retrieve/pii/002839089500098Q}}</ref> Originally developed as an [[antihypertensive|antihypertensive agent]],<ref name="pmid3207999"/><ref name="Pitchot W, Wauthy J, Legros JJ, Ansseau M 2004 151–5"/><ref name="pmid2842163">{{cite journal | author = Wouters W, Tulp MT, Bevan P | title = Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors | journal = European Journal of Pharmacology | volume = 149 | issue = 3 | pages = 213–23 | year = 1988 | month = May | pmid = 2842163 | doi = 10.1016/0014-2999(88)90651-6| url = }}</ref> it was later found to possess [[antidepressant]] and [[anxiolytic]] effects in animals.<ref name="pmid1351303">{{cite journal | author = van Hest A, van Drimmelen M, Olivier B | title = Flesinoxan shows antidepressant activity in a DRL 72-s screen | journal = Psychopharmacology | volume = 107 | issue = 4 | pages = 474–9 | year = 1992 | pmid = 1351303 | doi = 10.1007/BF02245258| url = }}</ref><ref name="pmid7972301">{{cite journal | author = Rodgers RJ, Cole JC, Davies A | title = Antianxiety and behavioral suppressant actions of the novel 5-HT1A receptor agonist, flesinoxan | journal = Pharmacology, Biochemistry, and Behavior | volume = 48 | issue = 4 | pages = 959–63 | year = 1994 | month = August | pmid = 7972301 | doi = 10.1016/0091-3057(94)90205-4| url = http://linkinghub.elsevier.com/retrieve/pii/0091-3057(94)90205-4}}</ref> As a result, it was investigated in [[human]] [[clinical trial]]s for the treatment of [[major depressive disorder]] and [[generalized anxiety disorder]] and was found to have robust [[efficacy]] with very high [[tolerability]],<ref name="pmid8263314">{{cite journal | author = Grof P, Joffe R, Kennedy S, Persad E, Syrotiuk J, Bradford D | title = An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression | journal = International Clinical Psychopharmacology | volume = 8 | issue = 3 | pages = 167–72 | year = 1993 | pmid = 8263314 | doi = 10.1097/00004850-199300830-00005| url = }}</ref><ref name="Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart 2004 279–283">{{cite journal | author = Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart | title = Pilot study of flesinoxan, a 5-HT1A agonist, in major depression: Effects on sleep REM latency and body temperature. | journal = Human Psychopharmacology: Clinical and Experimental | volume = 8 | issue = 4 | pages = 279–283 | year = 2004 | url = http://www3.interscience.wiley.com/journal/109710934/abstract | doi = 10.1002/hup.470080407 }}</ref> but for unclear reasons development was halted and it was never marketed. In patients it enhances [[Rapid eye movement sleep|REM]] [[sleep]] latency, decreases [[body temperature]], and increases [[adrenocorticotropic hormone|ACTH]], [[cortisol]], [[prolactin]], and [[growth hormone]] [[Cellular secretion|secretion]].<ref name="Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart 2004 279–283"/><ref name="pmid15013031">{{cite journal | author = Pitchot W, Wauthy J, Legros JJ, Ansseau M | title = Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study | journal = European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology | volume = 14 | issue = 2 | pages = 151–5 | year = 2004 | month = March | pmid = 15013031 | doi = 10.1016/S0924-977X(03)00108-1 | url = }}</ref>


== See also ==
== See also ==

Revision as of 22:47, 6 January 2011

{{Drugbox | IUPAC_name = 4-fluoro-N-(2-{4-[(2S)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-5-yl]piperazin-1-yl}ethyl)benzamide | image = Flesinoxan.svg | CAS_number = 98206-10-1 | ATC_prefix = none | ATC_suffix = | PubChem = 57347 | ChemSpiderID = 51700 | C = 22 | H = 26 | F = 1 | N = 3 | O = 4 | molecular_weight = 415.458 g/mol | smiles = C1CN(CCN1CCNC(=O)C2=CC=C(C=C2)F)C3=C4C(=CC=C3)O[C@H](CO4)CO | bioavailability = | metabolism = | elimination_half-life = | excretion = | pregnancy_category = | legal_status = Uncontrolled | routes_of_administration = Oral }}

Flesinoxan (DU-29,373) is a potent and selective 5-HT1A receptor partial/near-full agonist of the phenylpiperazine class.[1][2][3] Originally developed as an antihypertensive agent,[1][2][4] it was later found to possess antidepressant and anxiolytic effects in animals.[5][6] As a result, it was investigated in human clinical trials for the treatment of major depressive disorder and generalized anxiety disorder and was found to have robust efficacy with very high tolerability,[7][8] but for unclear reasons development was halted and it was never marketed. In patients it enhances REM sleep latency, decreases body temperature, and increases ACTH, cortisol, prolactin, and growth hormone secretion.[8][9]

See also

References

  1. ^ a b Schoeffter P, Hoyer D. (1988). "Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus". Br J Pharmacol. 95 (3): 975–985. PMC 1854240. PMID 3207999.
  2. ^ a b Pitchot W, Wauthy J, Legros JJ, Ansseau M (2004). "Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study". European Neuropsychopharmacology. 14 (2): 151–5. doi:10.1016/S0924-977X(03)00108-1. PMID 15013031. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Hadrava V, Blier P, Dennis T, Ortemann C, de Montigny C (1995). "Characterization of 5-hydroxytryptamine1A properties of flesinoxan: in vivo electrophysiology and hypothermia study". Neuropharmacology. 34 (10): 1311–26. doi:10.1016/0028-3908(95)00098-Q. PMID 8570029. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Wouters W, Tulp MT, Bevan P (1988). "Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors". European Journal of Pharmacology. 149 (3): 213–23. doi:10.1016/0014-2999(88)90651-6. PMID 2842163. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ van Hest A, van Drimmelen M, Olivier B (1992). "Flesinoxan shows antidepressant activity in a DRL 72-s screen". Psychopharmacology. 107 (4): 474–9. doi:10.1007/BF02245258. PMID 1351303.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Rodgers RJ, Cole JC, Davies A (1994). "Antianxiety and behavioral suppressant actions of the novel 5-HT1A receptor agonist, flesinoxan". Pharmacology, Biochemistry, and Behavior. 48 (4): 959–63. doi:10.1016/0091-3057(94)90205-4. PMID 7972301. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Grof P, Joffe R, Kennedy S, Persad E, Syrotiuk J, Bradford D (1993). "An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression". International Clinical Psychopharmacology. 8 (3): 167–72. doi:10.1097/00004850-199300830-00005. PMID 8263314.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ a b Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart (2004). "Pilot study of flesinoxan, a 5-HT1A agonist, in major depression: Effects on sleep REM latency and body temperature". Human Psychopharmacology: Clinical and Experimental. 8 (4): 279–283. doi:10.1002/hup.470080407.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Pitchot W, Wauthy J, Legros JJ, Ansseau M (2004). "Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study". European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 14 (2): 151–5. doi:10.1016/S0924-977X(03)00108-1. PMID 15013031. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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