Tiospirone
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| Metabolism | Hepatic |
| Biological half-life | 1.4 hours |
| Excretion | Urine |
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| Formula | C24H32N4O2S |
| Molar mass | 440.60 g/mol |
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 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]
- ^ Yevich JP, New JS, Smith DW, 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): 359–69. 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): 129–33. 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): 190–3. PMID 2574893.
- ^ Nasrallah, Henry A.; Shriqui, Christian L (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 & Pharmaceutical Bulletin. 43 (12): 2139–51. doi:10.1248/cpb.43.2139. PMID 8582016.
- ^ Sumiyoshi T, Suzuki K, Sakamoto H, et al. (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): 365–8. doi:10.1007/BF02311185. PMID 8524985.
- ^ Weiner DM, Burstein ES, Nash N, et al. (October 2001). "5-hydroxytryptamine2A receptor inverse agonists as antipsychotics". The Journal of Pharmacology and Experimental Therapeutics. 299 (1): 268–76. 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): 226–32. 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.
- ^ 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): 341–56. doi:10.1017/S1461145704005000. PMID 15707540.
- ^ 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. Retrieved 3 December 2013.
