Tandospirone

Tandospirone
Clinical data
Trade names Sediel
AHFS/Drugs.com International Drug Names
Routes of
administration		 Oral
ATC code none
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Biological half-life 2-3 hours (3-5 hours for active metabolite, pyrimidinylpiperazine)
Excretion Urine (70%; 0.1% as unchanged drug)
Identifiers
CAS Number 112457-95-1 N
PubChem (CID) 91273
IUPHAR/BPS 55
ChemSpider 82421 YesY
UNII 190230I669 YesY
ChEMBL CHEMBL274047 YesY
ECHA InfoCard 100.210.461
Chemical and physical data
Formula C21H29N5O2
Molar mass 383.487 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

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.

Medical uses

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

Common adverse effects include:[1]

Adverse effects with unknown frequency include:[1]

It is not believed to be addictive but it is known to produce mild withdrawal effects (e.g. anorexia) after abrupt discontinuation.[1]

Pharmacology

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

Synthesis

Tandospirone synthesis:[10][11]

The noreximide precursor also has dual uses to make taglutimide and tripamide.

See also

References

  1. 1 2 3 4 5 Barradell, LB; Fitton, A (February 1996). "Tandospirone". CNS Drugs (PDF). 5 (2): 147–153. doi:10.2165/00023210-199605020-00006.
  2. ↑ 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.
  3. ↑ Tandospirone. Martindale: The Complete Drug Reference. The Royal Pharmaceutical Society of Great Britain. 23 September 2011. Retrieved 14 November 2013.
  4. ↑ 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.
  5. 1 2 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.
  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.
  7. ↑ 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.
  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.
  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. doi:10.1097/00004714-199210000-00009. 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.; 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.
  11. ↑ EP 0082402


This article is issued from Wikipedia - version of the 11/8/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.