Tiospiron
| |||
| (IUPAC) ime | |||
|---|---|---|---|
| 8-[4-[4-(1,2-benzotiazol-3-il)piperazin-1-il]butil]-8-azaspiro[4.5]dekan-7,9-dion | |||
| Klinički podaci | |||
| Identifikatori | |||
| CAS broj | 87691-91-6 | ||
| ATC kod | nije dodeljen | ||
| PubChem[1][2] | 55752 | ||
| ChemSpider[3] | 50348 | ||
| UNII | 35C6UMO5SR 
| ||
| ChEMBL[4] | CHEMBL35057 | ||
| Hemijski podaci | |||
| Formula | C24H32N4O2S | ||
| Mol. masa | 440,60 g/mol | ||
| SMILES | eMolekuli & PubHem | ||
| |||
| Farmakokinetički podaci | |||
| Metabolizam | Hepatic | ||
| Poluvreme eliminacije | 1,4 sata | ||
| Izlučivanje | Urine | ||
| Farmakoinformacioni podaci | |||
| Trudnoća | ? | ||
| Pravni status | |||
Tiospiron (BMY-13,859, tiaspiron, tiosperon) je atipični antipsihotik iz azapironske klase.[5] On je istraživan kao tretman za šizofreniju tokom kasnih 1980-tih i poznato je da je efektivan ekvivalent tipičnih antipsihotika i da ne izaziva ekstrapiramidalne nuspojave.[6][7][8][9] Međutim, njegov razvoj je zaustavljen. Perospiron, jedan drugi derivat azapirona sa antipsihotičkim svojstvima, je sintetisan i karakterisan nekoliko godina kasnije.[10] Za njega je utvrđeno da je potentniji i selektivniji od tiospirona te je plasiran na tržište.[10]
Tiospiron deluje kao parcijalni agonist 5-HT1A receptora, inverzni agonist 5-HT2A, 5-HT2C, i 5-HT7 receptora, i antagonist D2, D4, i α1-adrenergičkog receptora.[11][12][13][14][15][16]
- ↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519.
- ↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
- ↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846.
- ↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594.
- ↑ 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. str. 313. ISBN 0-88048-681-3.
- ↑ 10,0 10,1 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 / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 8 (3): 341–56. DOI:10.1017/S1461145704005000. PMID 15707540.