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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/27 07:40:58」(JST)

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Tandospirone (Sediel), also known as metanopirone, is an anxiolytic and antidepressant used in China and Japan, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone and piperazine chemical classes and is closely related to other agents like buspirone and gepirone.

Pharmacology

Tandospirone acts as a potent and selective 5-HT_1A receptor partial agonist, with a K_i affinity value of 27 ± 5 nM^[1] and approximately 55-85% intrinsic activity.^[2]^[3] It has weak and clinically negligible affinity for the 5-HT_2A (1,300 ± 200), 5-HT_2C (2,600 ± 60), α₁-adrenergic (1,600 ± 80), α₂-adrenergic (1,900 ± 400), D₁ (41,000 ± 10,000), and D₂ (1,700 ± 300) receptors, and is essentially inactive at the 5-HT_1B, 5-HT_1D, β-adrenergic, and muscarinic acetylcholine receptors, serotonin transporter (SERT), and benzodiazepine (BDZ) allosteric site of the GABA_A receptor (all of which are > 100,000).^[1] There is evidence of tandospirone having low but significant antagonistic activity at the α₂-adrenergic receptor through its active metabolite 1-(2-pyrimidinyl)piperazine (1-PP), however.^[4]^[5]

Dosage

Tandospirone is typically used at a dose of 30 mg/daily^[6] taken in divided doses of 10 mg three times per day due to its short half-life. Though originally considered a relatively weak anxiolytic agent,^[6] a clinical study found that doubling the dose to 60 mg/daily resulted in a "remarkable anxiolytic effect with an early onset of action, and without significant adverse effects", as well as "excellent anxiolytic efficacy that is comparable to that of the benzodiazepines".^[6]^[7]

Side effects

Side effects of tandospirone and other 5-HT_1A partial agonists are relatively mild and may include nausea, diarrhea, headache, dizziness, and restlessness.^[8]

Chemistry

Yevich, Joseph P.; New, James S.; Smith, David W.; Lobeck, Walter G.; Catt, John D.; Minielli, Joseph L.; Eison, Michael S.; Taylor, Duncan P. et al. (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.

References

^ ^a ^b 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.
^ ^a ^b ^c Nishitsuji; To, H; Murakami, Y; Kodama, K; Kobayashi, D; Yamada, T; Kubo, C; Mine, K (2004). "Tandospirone in the treatment of generalised anxiety disorder and mixed anxiety-depression : results of a comparatively high dosage trial". Clinical drug investigation 24 (2): 121–6. PMID 17516698.
^ Evans; Troisi Jr, 2nd; Griffiths, RR (1994). "Tandospirone and alprazolam: comparison of behavioral effects and abuse liability in humans". The Journal of Pharmacology and Experimental Therapeutics 271 (2): 683–94. PMID 7965783.
^ Feighner JP, Boyer WF (1989). "Serotonin-1A anxiolytics: an overview". Psychopathology 22 Suppl 1: 21–6. PMID 2567039.

English Journal

The Application of the Rome IV Criteria to Functional Esophagogastroduodenal Disorders in Asia.

Suzuki H1.
Journal of neurogastroenterology and motility.J Neurogastroenterol Motil.2017 Jul 30;23(3):325-333. doi: 10.5056/jnm17018.
PMID 28672431

Photolytic and photocatalytic degradation of tandospirone: Determination of kinetics, identification of transformation products and in silico estimation of toxicity.

Trawiński J1, Skibiński R2.
The Science of the total environment.Sci Total Environ.2017 Jul 15;590-591:775-798. doi: 10.1016/j.scitotenv.2017.03.050. Epub 2017 Mar 11.
PMID 28292608

Rapid and highly sensitive analysis of benzodiazepines and tandospirone in human plasma by automated on-line column-switching UFLC-MS/MS.

Lee XP1, Shouji Y2, Kumazawa T3, Hasegawa C4, Fujishiro M2, Sato J2, Hasegawa I5, Sato K2.
Legal medicine (Tokyo, Japan).Leg Med (Tokyo).2017 Jan;24:36-55. doi: 10.1016/j.legalmed.2016.11.005. Epub 2016 Nov 27.
PMID 28081789

Japanese Journal

症例報告フルボキサミンとタンドスピロンによるセロトニン症候群により日本で初めて死亡した1例

川野貴久,小菅宇之,高木俊介 [他]
The Japanese journal of clinical toxicology 24(4), 305-310, 2011
NAID 40019125937

Tandospironeにより排泄に関する固執性が軽減した認知症患者の2例

佐藤晋爾,堤孝太,木村絵里子 [他]
精神医学 52(1), 65-68, 2010-01
NAID 40016905746

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★リンクテーブル★

リンク元	「セロトニン受容体」「ドパミン受容体」「タンドスピロン」
拡張検索	「tandospirone citrate」

「セロトニン受容体」

Tandospirone
Systematic (IUPAC) name
	(1R,2R,6S,7S)-4-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}-4-azatricyclo[5.2.1.02,6]decane-3,5-dione
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	℞ Prescription only
Routes	Oral
Pharmacokinetic data
Half-life	1.2–1.4 hours
Identifiers
CAS number	112457-95-1
ATC code	None
PubChem	CID 91273
IUPHAR ligand	55
ChemSpider	82421
UNII	190230I669
ChEMBL	CHEMBL274047
Chemical data
Formula	C21H29N5O2
Mol. mass	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 ;
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　　[★]

英: serotonin receptor
同: 5-HT受容体
関: セロトニン