Tandospiron

Tandospiron
(IUPAC) ime
	(1R,2R,6S,7S)-44-[4-(pirimidin-2-il)piperazin-1-il]butil4-azatriciklo[5.2.1.02,6]dekan-3,5-dion
Klinički podaci
AHFS/Drugs.com	Internacionalno ime leka
Identifikatori
CAS broj	112457-95-1
ATC kod	nije dodeljen
PubChem	91273
ChemSpider	82421
UNII	190230I669
ChEMBL	CHEMBL274047
Hemijski podaci
Formula	C21H29N5O2
Mol. masa	383,487 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C21H29N5O2/c27-19-17-15-4-5-16(14-15)18(17)20(28)26(19)9-2-1-8-24-10-12-25(13-11-24)21-22-6-3-7-23-21/h3,6-7,15-18H,1-2,4-5,8-14H2/t15-,16+,17+,18- ; Key: CEIJFEGBUDEYSX-FZDBZEDMSA-N
Farmakokinetički podaci
Poluvreme eliminacije	1,2–1,4 sata
Farmakoinformacioni podaci
Trudnoća	?
Pravni status	℞ Prescription only
Način primene	Oralno

Tandospiron (Sediel, metanopiron) je anksiolitik i antidepresiv koji se koristi u Kini i Japanu. On je član azapironske i piperazinske hemijske klase, i blisko je srodan sa drugim agensima poput buspirona i gepirona.

Farmakologija

Tandospiron deluje kao potentan i selektivan parcijalni agonist 5-HT_1A receptora, sa K_i afinitetom od 27 ± 5 nM^[5] i aproksimativno 55-85% intrinsične aktivnosti.^[6]^[7] On ima slab i klinički zanemarljiv afinitet za 5-HT_2A (1,300 ± 200), 5-HT_2C (2,600 ± 60), α₁-adrenergički (1,600 ± 80), α₂-adrenergički (1,900 ± 400), D₁ (41,000 ± 10,000), i D₂ (1,700 ± 300) receptore, i esencijalno je neaktivan na 5-HT_1B, 5-HT_1D, β-adrenergičkom, i muskarinskim acetilholinskim receptorima, serotoniskom transportertu (SERT), i benzodiazepinskom (BDZ) alosternom mestu GABA_A receptora (svi od kojih su > 100.000).^[5] Postoji evidencija da tandospiron ima nisku, mada značajnu antagonističku aktivnost na α₂-adrenergičkom receptoru putem njegovog aktivnog metabolita 1-(2-pirimidinil)piperazin (1-PP).^[8]^[9]

Hemija

Tandospiron se može sintetisati na sledeće način:^[10]

Reference

↑ 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. edit
↑ 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. edit
↑ 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. edit
↑ ^5,0 ^5,1 Hamik; Oksenberg, D; Fischette, C; Peroutka, SJ (1990). „Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites”. Biological Psychiatry 28 (2): 99–109. DOI:10.1016/0006-3223(90)90627-E. PMID 1974152.
↑ Tanaka; Tatsuno, T; Shimizu, H; Hirose, A; Kumasaka, Y; Nakamura, M (1995). „Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain”. General pharmacology 26 (8): 1765–72. DOI:10.1016/0306-3623(95)00077-1. PMID 8745167.
↑ Yabuuchi, Kazuki; Tagashira, Rie; Ohno, Yukihiro (2004). „Effects of tandospirone, a novel anxiolytic agent, on human 5-HT_1A receptors expressed in Chinese hamster ovary cells (CHO cells)”. Biogenic Amines 18 (3): 319. DOI:10.1163/1569391041501933.
↑ Blier; Curet, O; Chaput, Y; De Montigny, C (1991). „Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--II. Effects of acute administration of 1-PP and long-term administration of tandospirone on noradrenergic neurotransmission”. Neuropharmacology 30 (7): 691–701. DOI:10.1016/0028-3908(91)90176-C. PMID 1681447.
↑ Miller; Thompson, ML; Byrnes, JJ; Greenblatt, DJ; Shemer, A (1992). „Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine”. Journal of Clinical Psychopharmacology 12 (5): 341–5. PMID 1362206.
↑ Yevich, Joseph P.; New, James S.; Smith, David W.; Lobeck, Walter G.; Catt, John D.; Minielli, Joseph L.; Eison, Michael S.; Taylor, Duncan P. i dr.. (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.

Povezano

Vanjske veze

	Portal Medicina
	Portal Hemija

[1] 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. edit

[2] 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.

[3] 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. edit

[4] 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. edit

[pmid1974152-5] 5,0 ^5,1 Hamik; Oksenberg, D; Fischette, C; Peroutka, SJ (1990). „Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites”. Biological Psychiatry 28 (2): 99–109. DOI:10.1016/0006-3223(90)90627-E. PMID 1974152.

[pmid8745167-6] Tanaka; Tatsuno, T; Shimizu, H; Hirose, A; Kumasaka, Y; Nakamura, M (1995). „Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain”. General pharmacology 26 (8): 1765–72. DOI:10.1016/0306-3623(95)00077-1. PMID 8745167.

[journalEffects_of_tandospirone,_a_novel_anxiolytic_agent,_on_human_5-HT1...-7] Yabuuchi, Kazuki; Tagashira, Rie; Ohno, Yukihiro (2004). „Effects of tandospirone, a novel anxiolytic agent, on human 5-HT_1A receptors expressed in Chinese hamster ovary cells (CHO cells)”. Biogenic Amines 18 (3): 319. DOI:10.1163/1569391041501933.

[pmid1681447-8] Blier; Curet, O; Chaput, Y; De Montigny, C (1991). „Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--II. Effects of acute administration of 1-PP and long-term administration of tandospirone on noradrenergic neurotransmission”. Neuropharmacology 30 (7): 691–701. DOI:10.1016/0028-3908(91)90176-C. PMID 1681447.

[pmid1362206-9] Miller; Thompson, ML; Byrnes, JJ; Greenblatt, DJ; Shemer, A (1992). „Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine”. Journal of Clinical Psychopharmacology 12 (5): 341–5. PMID 1362206.

[10] Yevich, Joseph P.; New, James S.; Smith, David W.; Lobeck, Walter G.; Catt, John D.; Minielli, Joseph L.; Eison, Michael S.; Taylor, Duncan P. i dr.. (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.

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