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
Drugs.com	Internacionalno ime leka
Način primene	Oralno
Pravni status
Pravni status	℞ (Prescription only);
Farmakokinetički podaci
Poluvreme eliminacije	1,2–1,4 sata
Identifikatori
CAS broj	112457-95-1
ATC kod	none
PubChem	CID 91273
IUPHAR/BPS	55
ChemSpider	82421
UNII	190230I669
ChEMBL	CHEMBL274047
Hemijski podaci
Formula	C21H29N5O2
Molarna masa	383,487 g/mol
	SMILES O=C1N(C(=O)[C@H]3[C@@H]1[C@@H]2CC[C@H]3C2)CCCCN5CCN(c4ncccn4)CC5; ;
	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 ;

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^[1] i približno 55-85% intrinsične aktivnosti.^[2]^[3] 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).^[1] Postoji evidencija da tandospiron ima nisku, mada značajnu antagonističku aktivnost na α₂-adrenergičkom receptoru putem njegovog aktivnog metabolita 1-(2-pirimidinil)piperazin (1-PP).^[4]^[5]

Hemija

Tandospiron se može sintetisati na sledeće način:^[6]

Reference

^ ^а ^б 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. PMID 1974152. doi:10.1016/0006-3223(90)90627-E.
^ 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. PMID 8745167. doi:10.1016/0306-3623(95)00077-1.
^ 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. PMID 1681447. doi:10.1016/0028-3908(91)90176-C.
^ 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.; Riblet, Leslie A. (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. PMID 2869146. doi:10.1021/jm00153a010.

Vidi još

Spoljašnje veze

[pmid1974152-1] а ^б 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. PMID 1974152. doi:10.1016/0006-3223(90)90627-E.

[pmid8745167-2] 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. PMID 8745167. doi:10.1016/0306-3623(95)00077-1.

[journalEffects_of_tandospirone,_a_novel_anxiolytic_agent,_on_human_5-HT1...-3] 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.

[pmid1681447-4] 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. PMID 1681447. doi:10.1016/0028-3908(91)90176-C.

[pmid1362206-5] 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.

[6] Yevich, Joseph P.; New, James S.; Smith, David W.; Lobeck, Walter G.; Catt, John D.; Minielli, Joseph L.; Eison, Michael S.; Taylor, Duncan P.; Riblet, Leslie A. (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. PMID 2869146. doi:10.1021/jm00153a010.

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[2]

[3]

[4]

[5]

[6]

Farmakologija

Hemija

Reference

Vidi još

Spoljašnje veze

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