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 Uncontrolled
Routes Oral
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 Y
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 drug of the azapirone class.[1] It 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.[2][3][4][5][6][7]

Tiospirone was tested in clinical trials for the treatment of schizophrenia in the late 1980s, and was found to have efficacy equivalent to that of typical antipsychotics without causing extrapyramidal side effects.[8][9][10][11] However, development was not continued and it was never marketed.

Perospirone, another azapirone derivative with antipsychotic properties, was synthesized and assayed several years after tiospirone.[12] It was found to be both more potent and more selective in comparison and was commercialized instead.[12]

See also

References

  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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11561089. 
  5. ^ 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. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10991983. 
  6. ^ 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. 
  7. ^ 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. http://journals.cambridge.org/abstract_S1461145704005000. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. http://books.google.com/?id=ut79yW-IZx4C&lpg=PA313&dq=tiospirone%20adrenergic&pg=PA313#v=onepage&q=&f=false. 
  12. ^ 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. PMID 8582016. 
Antipsychotics (neuroleptics) (N05A)
Typical
Benzamides: Levosulpiride • Nemonapride • Sulpiride • Sultopride • Tiapride • Veralipride; Butyrophenones: Azaperone • Benperidol • Bromperidol • Droperidol • Fluanisone • Haloperidol • Lenperone • Moperone • Pipamperone • Spiperone • Timiperone • Trifluperidol; Diphenylbutylpiperidines: Clopimozide • Fluspirilene • Penfluridol • Pimozide; Phenothiazines: Acepromazine • Acetophenazine • Butaperazine • Carphenazine • Chloracizine • Chlorproethazine • Chlorpromazine • Cyamemazine • Dixyrazine • Fluacizine • Fluphenazine • Levomepromazine/Methotrimeprazine • Mesoridazine • Perazine • Pericyazine • Perphenazine • Piperacetazine • Pipotiazine • Prochlorperazine • Promazine • Promethazine • Propiomazine • Sulforidazine • Thiethylperazine • Thiopropazate • Thioproperazine • Thioridazine • Trifluoperazine • Triflupromazine; Thioxanthenes: Chlorprothixene • Clopenthixol • Flupentixol • Thiothixene • Zuclopenthixol; Tricyclics: Amoxapine • Butaclamol • Fluotracen • Loxapine • Trimipramine; Others: Prothipendyl
Atypical
Others

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc(eval/thrp), drug(N5A/5B/5C/6A/6B/6D)