Tiospirone Explained

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

Notes and References

  1. Yevich JP, New JS, Smith DW, Lobeck WG, Catt JD, Minielli JL, Eison MS, Taylor DP, Riblet LA, Temple DL . 6 . 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 . 2869146 . 10.1021/jm00153a010 .
  2. Jain AK, Kelwala S, Moore N, Gershon S . A controlled clinical trial of tiaspirone in schizophrenia . International Clinical Psychopharmacology . 2 . 2 . 129–133 . April 1987 . 2885367 . 10.1097/00004850-198704000-00006 .
  3. Moore NC, Meyendorff E, Yeragani V, LeWitt PA, Gershon S . Tiaspirone in schizophrenia . Journal of Clinical Psychopharmacology . 7 . 2 . 98–101 . April 1987 . 3294920 . 10.1097/00004714-198704000-00010 .
  4. Borison RL, Sinha D, Haverstock S, McLarnon MC, Diamond BI . Efficacy and safety of tiospirone vs. haloperidol and thioridazine in a double-blind, placebo-controlled trial . Psychopharmacology Bulletin . 25 . 2 . 190–193 . 1989 . 2574893 .
  5. Book: Nasrallah HA, Shriqui CL . Contemporary issues in the treatment of schizophrenia . American Psychiatric Press . Washington, DC . 1995 . 313 . 0-88048-681-3 .
  6. Ishizumi K, Kojima A, Antoku F, Saji I, Yoshigi M . 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 . 8582016 . 10.1248/cpb.43.2139 . free .
  7. Sumiyoshi T, Suzuki K, Sakamoto H, Yamaguchi N, Mori H, Shiba K, Yokogawa K . Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy . Neuropsychopharmacology . 12 . 1 . 57–64 . February 1995 . 7766287 . 10.1016/0893-133X(94)00064-7 .
  8. Roth BL, Tandra S, Burgess LH, Sibley DR, Meltzer HY . D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs . Psychopharmacology . 120 . 3 . 365–368 . August 1995 . 8524985 . 10.1007/BF02311185 . 13549491 . Bryan Roth .
  9. Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, Harvey SC, Donohue E, Hansen HC, Andersson CM, Spalding TA, Gibson DF, Krebs-Thomson K, Powell SB, Geyer MA, Hacksell U, Brann MR . 6 . 5-hydroxytryptamine2A receptor inverse agonists as antipsychotics . The Journal of Pharmacology and Experimental Therapeutics . 299 . 1 . 268–276 . October 2001 . 11561089 .
  10. Herrick-Davis K, Grinde E, Teitler M . 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 . 10991983 .
  11. Rauly-Lestienne I, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Cussac D . 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 . 17786406 . 10.1007/s00210-007-0182-6 . 29337002 .
  12. Newman-Tancredi A, Assié MB, Leduc N, Ormière AM, Danty N, Cosi C . 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 . 15707540 . 10.1017/S1461145704005000 . 36271263 .
  13. Web site: PDSP Ki Database . Psychoactive Drug Screening Program (PDSP) . Roth BL, Driscol J . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 3 December 2013 . 12 January 2011 . dead . https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php . 8 November 2013 .

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