Tiospirone

Tiospirone
Systematic (IUPAC) name
	8-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione
Clinical data
Pregnancy cat.	?
Legal status	?
Pharmacokinetic data
Metabolism	Hepatic
Half-life	1.4 hours
Excretion	Urine
Identifiers
CAS number	87691-91-6
ATC code	None
PubChem	CID 55752
IUPHAR ligand	101
ChemSpider	50348
UNII	35C6UMO5SR
ChEMBL	CHEMBL35057
Chemical data
Formula	C24H32N4O2S
Mol. 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-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]

[edit] See also

Azapirone

[edit] References

^ 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. 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. ISBN [[Special:BookSources/0021000701826|0021000701826 [[Category:Articles with invalid ISBNs]] [[Category:Articles with invalid ISBNs]]]] Check |isbn= value (help). 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 / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 8 (3): 341–56. doi:10.1017/S1461145704005000. PMID 15707540.

[pmid2869146-1] 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.

[pmid2885367-2] Jain AK, Kelwala S, Moore N, Gershon S (April 1987). "A controlled clinical trial of tiaspirone in schizophrenia". International Clinical Psychopharmacology 2 (2): 129–33. doi:10.1097/00004850-198704000-00006. PMID 2885367.

[pmid3294920-3] Moore NC, Meyendorff E, Yeragani V, LeWitt PA, Gershon S (April 1987). "Tiaspirone in schizophrenia". Journal of Clinical Psychopharmacology 7 (2): 98–101. PMID 3294920.

[pmid2574893-4] 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): 190–3. PMID 2574893.

[isbn0-88048-681-3-5] 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.

[pmid8582016-6] 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): 2139–51. doi:10.1248/cpb.43.2139. PMID 8582016.

[pmid7766287-7] 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.

[pmid8524985-8] 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): 365–8. doi:10.1007/BF02311185. PMID 8524985.

[pmid11561089-9] 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.

[pmid10991983-10] 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): 226–32. PMID 10991983.

[pmid17786406-11] 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. ISBN [[Special:BookSources/0021000701826|0021000701826 [[Category:Articles with invalid ISBNs]] [[Category:Articles with invalid ISBNs]]]] Check |isbn= value (help). PMID 17786406.

[pmid15707540-12] 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 / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 8 (3): 341–56. doi:10.1017/S1461145704005000. PMID 15707540.

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Tiospirone

[edit] See also

[edit] References

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