Tandospirone

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Tandospirone
Tandospirone.svg
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
Trade names Sediel
AHFS/Drugs.com International Drug Names
Legal status
  • Prescription only
Routes Oral
Pharmacokinetic data
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
ATC code None
PubChem CID 91273
IUPHAR ligand 55
ChemSpider 82421 YesY
UNII 190230I669 YesY
ChEMBL CHEMBL274047 YesY
Chemical data
Formula C21H29N5O2 
Molecular mass 383.487 g/mol
 N (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[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]

  • 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]

Chemistry[edit]

Tandospirone synth.png

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. 

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 (SERT), and benzodiazepine (BDZ) 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]

See also[edit]

References[edit]

  1. ^ 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. 
  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. ^ 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. 
  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.