Chemistry:Tiospirone

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Short description: Atypical antipsychotic drug
Tiospirone
Tiospirone.svg
Clinical data
ATC code
  • none
Legal status
Legal status
  • Development terminated
Pharmacokinetic data
MetabolismHepatic
Elimination half-life1.4 hours
ExcretionUrine
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC24H32N4O2S
Molar mass440.61 g·mol−1

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]

Pharmacology

Pharmacodynamics

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

References

  1. ↑ "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. March 1986. doi:10.1021/jm00153a010. PMID 2869146. 
  2. ↑ "A controlled clinical trial of tiaspirone in schizophrenia". International Clinical Psychopharmacology 2 (2): 129–133. April 1987. doi:10.1097/00004850-198704000-00006. PMID 2885367. 
  3. ↑ "Tiaspirone in schizophrenia". Journal of Clinical Psychopharmacology 7 (2): 98–101. April 1987. doi:10.1097/00004714-198704000-00010. PMID 3294920. 
  4. ↑ "Efficacy and safety of tiospirone vs. haloperidol and thioridazine in a double-blind, placebo-controlled trial". Psychopharmacology Bulletin 25 (2): 190–193. 1989. PMID 2574893. 
  5. ↑ Contemporary issues in the treatment of schizophrenia. Washington, DC: American Psychiatric Press. 1995. p. 313. ISBN 0-88048-681-3. https://books.google.com/books?id=ut79yW-IZx4C&q=tiospirone%20adrenergic&pg=PA313. 
  6. ↑ 6.0 6.1 "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. December 1995. doi:10.1248/cpb.43.2139. PMID 8582016. 
  7. ↑ "Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy". Neuropsychopharmacology 12 (1): 57–64. February 1995. doi:10.1016/0893-133X(94)00064-7. PMID 7766287. 
  8. ↑ "D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs". Psychopharmacology 120 (3): 365–368. August 1995. doi:10.1007/BF02311185. PMID 8524985. 
  9. ↑ "5-hydroxytryptamine2A receptor inverse agonists as antipsychotics". The Journal of Pharmacology and Experimental Therapeutics 299 (1): 268–276. October 2001. PMID 11561089. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11561089. 
  10. ↑ "Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors". The Journal of Pharmacology and Experimental Therapeutics 295 (1): 226–232. October 2000. PMID 10991983. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10991983. 
  11. ↑ "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. October 2007. doi:10.1007/s00210-007-0182-6. PMID 17786406. 
  12. ↑ "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. September 2005. doi:10.1017/S1461145704005000. PMID 15707540. 
  13. ↑ "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. 12 January 2011. http://pdsp.med.unc.edu/pdsp.php. 



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