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Tiospirone

May 08, 2024

Tiospirone (BMY-13,859), also sometimes called tiaspirone or tiosperone, is an atypical antipsychotic of the azapirone class.[1] It was investigated as a treatment for schizophrenia in the late 1980s and was found to have an effectiveness equivalent to those of typical antipsychotics in clinical trials but without causing extrapyramidal side effects.[2][3][4][5] However, development was halted and it was not marketed. Perospirone, another azapirone derivative with antipsychotic properties, was synthesized and assayed several years after tiospirone.[6] It was found to be both more potent and more selective in comparison and was commercialized instead.[6]

Tiospirone
Clinical data
ATC code
  • none
Legal status
Legal status
  • Development terminated
Pharmacokinetic data
MetabolismHepatic
Elimination half-life1.4 hours
ExcretionUrine
Identifiers
  • 8-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione
CAS Number
  • 87691-91-6
PubChem CID
  • 55752
IUPHAR/BPS
  • 101
ChemSpider
  • 50348
UNII
  • 35C6UMO5SR
ChEMBL
  • ChEMBL35057
CompTox Dashboard (EPA)
  • DTXSID90236558
Chemical and physical data
FormulaC24H32N4O2S
Molar mass440.61 g·mol−1

Pharmacology edit

Pharmacodynamics edit

Tiospirone acts as a 5-HT1A receptor partial agonist, 5-HT2A, 5-HT2C, and 5-HT7 receptor inverse agonist, and D2, D4, and α1-adrenergic receptor antagonist.[7][8][9][10][11][12]

Binding profile[13]

Receptor Ki (nM)
5-HT2A 0.06
5-HT2C 9.73
5-HT6 950
5-HT7 0.64
M1 630
M2 180
M3 1290
M4 480
M5 3900
D2 0.5
D4 13.6

See also edit

References edit

  1. ^ Yevich JP, New JS, Smith DW, Lobeck WG, Catt JD, Minielli JL, et al. (March 1986). "Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents". Journal of Medicinal Chemistry. 29 (3): 359–369. doi:10.1021/jm00153a010. PMID 2869146.
  2. ^ Jain AK, Kelwala S, Moore N, Gershon S (April 1987). "A controlled clinical trial of tiaspirone in schizophrenia". International Clinical Psychopharmacology. 2 (2): 129–133. doi:10.1097/00004850-198704000-00006. PMID 2885367.
  3. ^ Moore NC, Meyendorff E, Yeragani V, LeWitt PA, Gershon S (April 1987). "Tiaspirone in schizophrenia". Journal of Clinical Psychopharmacology. 7 (2): 98–101. doi:10.1097/00004714-198704000-00010. PMID 3294920.
  4. ^ Borison RL, Sinha D, Haverstock S, McLarnon MC, Diamond BI (1989). "Efficacy and safety of tiospirone vs. haloperidol and thioridazine in a double-blind, placebo-controlled trial". Psychopharmacology Bulletin. 25 (2): 190–193. PMID 2574893.
  5. ^ Nasrallah HA, Shriqui CL (1995). Contemporary issues in the treatment of schizophrenia. Washington, DC: American Psychiatric Press. p. 313. ISBN 0-88048-681-3.
  6. ^ a b Ishizumi K, Kojima A, Antoku F, Saji I, Yoshigi M (December 1995). "Succinimide derivatives. II. Synthesis and antipsychotic activity of N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-1,2-cis- cyclohexanedicarboximide (SM-9018) and related compounds". Chemical & Pharmaceutical Bulletin. 43 (12): 2139–2151. doi:10.1248/cpb.43.2139. PMID 8582016.
  7. ^ Sumiyoshi T, Suzuki K, Sakamoto H, Yamaguchi N, Mori H, Shiba K, Yokogawa K (February 1995). "Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy". Neuropsychopharmacology. 12 (1): 57–64. doi:10.1016/0893-133X(94)00064-7. PMID 7766287.
  8. ^ Roth BL, Tandra S, Burgess LH, Sibley DR, Meltzer HY (August 1995). "D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs". Psychopharmacology. 120 (3): 365–368. doi:10.1007/BF02311185. PMID 8524985. S2CID 13549491.
  9. ^ Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, et al. (October 2001). "5-hydroxytryptamine2A receptor inverse agonists as antipsychotics". The Journal of Pharmacology and Experimental Therapeutics. 299 (1): 268–276. PMID 11561089.
  10. ^ Herrick-Davis K, Grinde E, Teitler M (October 2000). "Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors". The Journal of Pharmacology and Experimental Therapeutics. 295 (1): 226–232. PMID 10991983.
  11. ^ Rauly-Lestienne I, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Cussac D (October 2007). "Differential profile of typical, atypical and third generation antipsychotics at human 5-HT7a receptors coupled to adenylyl cyclase: detection of agonist and inverse agonist properties". Naunyn-Schmiedeberg's Archives of Pharmacology. 376 (1–2): 93–105. doi:10.1007/s00210-007-0182-6. PMID 17786406. S2CID 29337002.
  12. ^ Newman-Tancredi A, Assié MB, Leduc N, Ormière AM, Danty N, Cosi C (September 2005). "Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia". The International Journal of Neuropsychopharmacology. 8 (3): 341–356. doi:10.1017/S1461145704005000. PMID 15707540. S2CID 36271263.
  13. ^ Roth BL, Driscol J (12 January 2011). . Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 3 December 2013.

May 08, 2024
tiospirone, also, sometimes, called, tiaspirone, tiosperone, atypical, antipsychotic, azapirone, class, investigated, treatment, schizophrenia, late, 1980s, found, have, effectiveness, equivalent, those, typical, antipsychotics, clinical, trials, without, caus. Tiospirone BMY 13 859 also sometimes called tiaspirone or tiosperone is an atypical antipsychotic of the azapirone class 1 It was investigated as a treatment for schizophrenia in the late 1980s and was found to have an effectiveness equivalent to those of typical antipsychotics in clinical trials but without causing extrapyramidal side effects 2 3 4 5 However development was halted and it was not marketed Perospirone another azapirone derivative with antipsychotic properties was synthesized and assayed several years after tiospirone 6 It was found to be both more potent and more selective in comparison and was commercialized instead 6 TiospironeClinical dataATC codenoneLegal statusLegal statusDevelopment terminatedPharmacokinetic dataMetabolismHepaticElimination half life1 4 hoursExcretionUrineIdentifiersIUPAC name 8 4 4 1 2 benzothiazol 3 yl piperazin 1 yl butyl 8 azaspiro 4 5 decane 7 9 dioneCAS Number87691 91 6PubChem CID55752IUPHAR BPS101ChemSpider50348UNII35C6UMO5SRChEMBLChEMBL35057CompTox Dashboard EPA DTXSID90236558Chemical and physical dataFormulaC 24H 32N 4O 2SMolar mass440 61 g mol 1 Contents 1 Pharmacology 1 1 Pharmacodynamics 2 See also 3 ReferencesPharmacology editPharmacodynamics edit Tiospirone acts as a 5 HT1A receptor partial agonist 5 HT2A 5 HT2C and 5 HT7 receptor inverse agonist and D2 D4 and a1 adrenergic receptor antagonist 7 8 9 10 11 12 Binding profile 13 Receptor Ki nM 5 HT2A 0 06 5 HT2C 9 73 5 HT6 950 5 HT7 0 64 M1 630 M2 180 M3 1290 M4 480 M5 3900 D2 0 5 D4 13 6See also editAzapironeReferences edit Yevich JP New JS Smith DW Lobeck WG Catt JD Minielli JL et al March 1986 Synthesis and biological evaluation of 1 1 2 benzisothiazol 3 yl and 1 2 benzisoxazol 3 yl piperazine derivatives as potential antipsychotic agents Journal of Medicinal Chemistry 29 3 359 369 doi 10 1021 jm00153a010 PMID 2869146 Jain AK Kelwala S Moore N Gershon S April 1987 A controlled clinical trial of tiaspirone in schizophrenia International Clinical Psychopharmacology 2 2 129 133 doi 10 1097 00004850 198704000 00006 PMID 2885367 Moore NC Meyendorff E Yeragani V LeWitt PA Gershon S April 1987 Tiaspirone in schizophrenia Journal of Clinical Psychopharmacology 7 2 98 101 doi 10 1097 00004714 198704000 00010 PMID 3294920 Borison RL Sinha D Haverstock S McLarnon MC Diamond BI 1989 Efficacy and safety of tiospirone vs haloperidol and thioridazine in a double blind placebo controlled trial Psychopharmacology Bulletin 25 2 190 193 PMID 2574893 Nasrallah HA Shriqui CL 1995 Contemporary issues in the treatment of schizophrenia Washington DC American Psychiatric Press p 313 ISBN 0 88048 681 3 a b Ishizumi K Kojima A Antoku F Saji I Yoshigi M December 1995 Succinimide derivatives II Synthesis and antipsychotic activity of N 4 4 1 2 benzisothiazol 3 yl 1 piperazinyl butyl 1 2 cis cyclohexanedicarboximide SM 9018 and related compounds Chemical amp Pharmaceutical Bulletin 43 12 2139 2151 doi 10 1248 cpb 43 2139 PMID 8582016 Sumiyoshi T Suzuki K Sakamoto H Yamaguchi N Mori H Shiba K Yokogawa K February 1995 Atypicality of several antipsychotics on the basis of in vivo dopamine D2 and serotonin 5HT2 receptor occupancy Neuropsychopharmacology 12 1 57 64 doi 10 1016 0893 133X 94 00064 7 PMID 7766287 Roth BL Tandra S Burgess LH Sibley DR Meltzer HY August 1995 D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs Psychopharmacology 120 3 365 368 doi 10 1007 BF02311185 PMID 8524985 S2CID 13549491 Weiner DM Burstein ES Nash N Croston GE Currier EA Vanover KE et al October 2001 5 hydroxytryptamine2A receptor inverse agonists as antipsychotics The Journal of Pharmacology and Experimental Therapeutics 299 1 268 276 PMID 11561089 Herrick Davis K Grinde E Teitler M October 2000 Inverse agonist activity of atypical antipsychotic drugs at human 5 hydroxytryptamine2C receptors The Journal of Pharmacology and Experimental Therapeutics 295 1 226 232 PMID 10991983 Rauly Lestienne I Boutet Robinet E Ailhaud MC Newman Tancredi A Cussac D October 2007 Differential profile of typical atypical and third generation antipsychotics at human 5 HT7a receptors coupled to adenylyl cyclase detection of agonist and inverse agonist properties Naunyn Schmiedeberg s Archives of Pharmacology 376 1 2 93 105 doi 10 1007 s00210 007 0182 6 PMID 17786406 S2CID 29337002 Newman Tancredi A Assie MB Leduc N Ormiere AM Danty N Cosi C September 2005 Novel antipsychotics activate recombinant human and native rat serotonin 5 HT1A receptors affinity efficacy and potential implications for treatment of schizophrenia The International Journal of Neuropsychopharmacology 8 3 341 356 doi 10 1017 S1461145704005000 PMID 15707540 S2CID 36271263 Roth BL Driscol J 12 January 2011 PDSP Ki Database Psychoactive Drug Screening Program PDSP University of North Carolina at Chapel Hill and the United States National Institute of Mental Health Archived from the original on 8 November 2013 Retrieved 3 December 2013 Retrieved from https en wikipedia org w index php title Tiospirone amp oldid 1191400944, wikipedia, wiki, book, books, library,

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