Tiospirone

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]

ATC code

none

Legal status

Development terminated

MetabolismHepatic

Elimination half-life1.4 hours

Quick facts Clinical data, ATC code ...

Tiospirone
Clinical data

ATC code	none
Legal status
Legal status	Development terminated
Pharmacokinetic data
Metabolism	Hepatic
Elimination half-life	1.4 hours
Excretion	Urine
Identifiers
IUPAC name 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
Formula	C₂₄H₃₂N₄O₂S
Molar mass	440.61 g·mol⁻¹

Pharmacology

Pharmacodynamics

Tiospirone acts as a 5-HT_1A receptor partial agonist, 5-HT_2A, 5-HT_2C, and 5-HT₇ receptor inverse agonist, and D₂, D₄, and α₁-adrenergic receptor antagonist.^[7]^[8]^[9]^[10]^[11]^[12]

Binding profile^[13]

More information Receptor, Ki (nM) ...

Receptor	K_i (nM)
5-HT_2A	0.06
5-HT_2C	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

References

[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]
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). "PDSP K_i 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.

Pharmacology

Pharmacodynamics

See also

References

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