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
Routes of
administration
Oral
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
ATC code none
PubChem CID 91273
IUPHAR/BPS 55
ChemSpider 82421 YesY
UNII 190230I669 YesY
ChEMBL CHEMBL274047 YesY
Chemical data
Formula C21H29N5O2
Molar mass 383.487 g/mol
 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[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]

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

Synthesis[edit]

Tandospirone synthesis:[5][6]

Pharmacology[edit]

Tandospirone acts as a potent and selective 5-HT1A receptor partial agonist, with a Ki affinity value of 27 ± 5 nM[7] and approximately 55-85% intrinsic activity.[8][9] 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).[7] 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.[10][11]

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. ^ 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. 
  6. ^ EP 0082402 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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.