Tandospirone
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| Clinical data | |
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| Trade names | Sediel |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration |
Oral |
| ATC code | none |
| Legal status | |
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| Pharmacokinetic data | |
| Biological half-life | 2-3 hours (3-5 hours for active metabolite, pyrimidinylpiperazine) |
| Excretion | Urine (70%; 0.1% as unchanged drug) |
| Identifiers | |
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| CAS Number | 112457-95-1  |
| PubChem (CID) | 91273 |
| IUPHAR/BPS | 55 |
| ChemSpider | 82421  |
| UNII | 190230I669 |
| ChEMBL | CHEMBL274047 |
| ECHA InfoCard | 100.210.461 |
| Chemical and physical data | |
| Formula | C21H29N5O2 |
| Molar mass | 383.487 g/mol |
| 3D model (Jmol) | Interactive image |
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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.
Contents
Medical uses[edit]
Tandospirone is most commonly used as a treatment for anxiety and depressive disorders, such as generalised anxiety disorder and dysthymia respectively.[1] For both indications it usually takes a couple of weeks for therapeutic effects to be start being seen,[1] although at higher doses more rapid anxiolytic responses have been seen.[2] It has also been used successfully as a treatment for bruxism.[3]
Tandospirone has also been tried, successfully, as an adjunctive treatment for cognitive symptoms in schizophrenic individuals.[4]
Adverse effects[edit]
Common adverse effects include:[1]
- Dizziness
- Drowsiness
- Insomnia
- Headache
- Gastrointestinal disorders
- Dry mouth
Adverse effects with unknown frequency include:[1]
- Hypotension (low blood pressure)
- Dysphoria
- Tachycardia
- Malaise
- Psychomotor impairment
It is not believed to be addictive but it is known to produce mild withdrawal effects (e.g. anorexia) after abrupt discontinuation.[1]
Pharmacology[edit]
Tandospirone acts as a potent and selective 5-HT1A receptor partial agonist, with a Ki affinity value of 27 ± 5 nM[5] and approximately 55-85% intrinsic activity.[6][7] It has weak and clinically negligible affinity for the 5-HT2A (1,300 ± 200), 5-HT2C (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-HT1B, 5-HT1D, β-adrenergic, and muscarinic acetylcholine receptors, serotonin transporter, and benzodiazepine allosteric site of the GABAA receptor (all of which are > 100,000).[5] 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.[8][9]
Chemistry[edit]
Synthesis[edit]
The noreximide precursor also has dual uses to make taglutimide and tripamide.
See also[edit]
References[edit]
- ^ a b c d e Barradell, LB; Fitton, A (February 1996). "Tandospirone". CNS Drugs (PDF). 5 (2): 147–153. doi:10.2165/00023210-199605020-00006.
- ^ 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 (PDF). 24 (2): 121–6. doi:10.2165/00044011-200424020-00007. PMID 17516698.
- ^ Tandospirone. Martindale: The Complete Drug Reference. The Royal Pharmaceutical Society of Great Britain. 23 September 2011. Retrieved 14 November 2013.
- ^ Sumiyoshi, T; Matsui, M; Nohara, S; Yamashita, I; Kurachi, M; Sumiyoshi, C; Jayathilake, K; Meltzer, HY (October 2001). "Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment" (PDF). The American Journal of Psychiatry. 158 (10): 1722–1725. doi:10.1176/appi.ajp.158.10.1722. PMID 11579010.
- ^ 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-HT1A 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. doi:10.1097/00004714-199210000-00009. 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.; 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.
- ^ EP 0082402
