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'''Tandospirone''' (brand name '''Sediel''') is an [[anxiolytic]] and [[antidepressant]] [[drug]] used in [[China]] and [[Japan]], where it is marketed by [[Dainippon Sumitomo Pharma]]. It is a member of the [[azapirone]] class of drugs and is closely related to other azapirones like [[buspirone]] and [[gepirone]].
'''Tandospirone''', sold under the brand name '''Sediel''', is an [[anxiolytic]] and [[antidepressant]] [[medication]] used in [[Japan]] and [[China]], where it is marketed by [[Dainippon Sumitomo Pharma]]. It is a member of the [[azapirone]] class of drugs and is closely related to other azapirones like [[buspirone]] and [[gepirone]].

Tandospirone was introduced for medical use in Japan in 1996<ref name="BrileyNutt2012" /> and in China in 2004.<ref name="RiedererLauxNagatsuLe2022" />


==Medical uses==
==Medical uses==
Line 57: Line 59:


===Other uses===
===Other uses===

Tandospirone has been tried successfully as an adjunctive treatment for cognitive symptoms{{clarify|date=July 2022}} in [[schizophrenia |schizophrenic]] individuals.<ref>{{cite journal | vauthors = Sumiyoshi T, Matsui M, Nohara S, Yamashita I, Kurachi M, Sumiyoshi C, Jayathilake K, Meltzer HY | display-authors = 6 | title = Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment | journal = The American Journal of Psychiatry | volume = 158 | issue = 10 | pages = 1722–1725 | date = October 2001 | pmid = 11579010 | doi = 10.1176/appi.ajp.158.10.1722 }}</ref>
Tandospirone has been tried successfully as an adjunctive treatment for cognitive symptoms{{clarify|date=July 2022}} in [[schizophrenia |schizophrenic]] individuals.<ref>{{cite journal | vauthors = Sumiyoshi T, Matsui M, Nohara S, Yamashita I, Kurachi M, Sumiyoshi C, Jayathilake K, Meltzer HY | display-authors = 6 | title = Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment | journal = The American Journal of Psychiatry | volume = 158 | issue = 10 | pages = 1722–1725 | date = October 2001 | pmid = 11579010 | doi = 10.1176/appi.ajp.158.10.1722 }}</ref>


==Side effects==
==Side effects==
Common adverse effects include:<ref name = CNS/>
Common adverse effects include:<ref name = CNS/><ref name="BrileyNutt2012" />


* Dizziness
* Dizziness
Line 70: Line 71:
* Dry mouth
* Dry mouth
* Negative influence on explicit memory function<ref name = CNS/>
* Negative influence on explicit memory function<ref name = CNS/>
* Nausea<ref name="BrileyNutt2012" />

Adverse effects with unknown frequency include:<ref name = CNS/>
Adverse effects with unknown frequency include:<ref name = CNS/>


Line 78: Line 81:
* [[Psychomotor impairment]]
* [[Psychomotor impairment]]


It is not believed to be addictive but is known to produce mild withdrawal effects (e.g., [[Anorexia (symptom)|anorexia]]) after abrupt discontinuation.<ref name = CNS/>
It is not believed to be addictive but is known to produce mild withdrawal effects (e.g., [[anorexia (symptom)|anorexia]]) after abrupt discontinuation.<ref name = CNS/>


==Pharmacology==
==Pharmacology==
Line 85: Line 88:
Tandospirone acts as a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[partial agonist]], with a [[dissociation constant|K<sub>i</sub>]] [[affinity (pharmacology)|affinity]] value of 27 ± 5 nM<ref name="pmid1974152">{{cite journal | vauthors = Hamik A, Oksenberg D, Fischette C, Peroutka SJ | title = Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites | journal = Biological Psychiatry | volume = 28 | issue = 2 | pages = 99–109 | date = July 1990 | pmid = 1974152 | doi = 10.1016/0006-3223(90)90627-E | s2cid = 25608914 }}</ref> and approximately 55 to 85% [[intrinsic activity]].<ref name="pmid8745167">{{cite journal | vauthors = Tanaka H, Tatsuno T, Shimizu H, Hirose A, Kumasaka Y, Nakamura M | title = Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain | journal = General Pharmacology | volume = 26 | issue = 8 | pages = 1765–1772 | date = December 1995 | pmid = 8745167 | doi = 10.1016/0306-3623(95)00077-1 }}</ref><ref name="Yabuuchi_2004">{{cite journal | vauthors = Yabuuchi K, Tagashira R, Ohno Y |title=Effects of tandospirone, a novel anxiolytic agent, on human 5-HT<SUB>1A</SUB> receptors expressed in Chinese hamster ovary cells (CHO cells) |journal=Biogenic Amines |year=2004 |volume=18 |issue=3 |pages=319–328 |doi=10.1163/1569391041501933}}</ref> It has relatively weak affinity for the [[5-HT2A receptor|5-HT<sub>2A</sub>]] (1,300 ± 200), [[5-HT2C receptor|5-HT<sub>2C</sub>]] (2,600 ± 60), [[alpha-1 adrenergic|α<sub>1</sub>-adrenergic]] (1,600 ± 80), [[alpha-2 adrenergic|α<sub>2</sub>-adrenergic]] (1,900 ± 400), [[D1 receptor|D<sub>1</sub>]] (41,000 ± 10,000), and [[D2 receptor|D<sub>2</sub>]] (1,700 ± 300) [[receptor (biochemistry)|receptor]]s, and is essentially inactive at the [[5-HT1B receptor|5-HT<sub>1B</sub>]], [[5-HT1D receptor|5-HT<sub>1D</sub>]], [[beta-adrenergic|β-adrenergic]], and [[muscarinic acetylcholine receptor]]s, [[serotonin transporter]], and [[benzodiazepine]] [[allosteric site]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]] (all of which are > 100,000).<ref name="pmid1974152" /> There is evidence of tandospirone having low but significant [[antagonist]]ic activity at the [[alpha-2 adrenergic|α<sub>2</sub>-adrenergic receptor]] through its active [[metabolite]] [[1-(2-pyrimidinyl)piperazine]] (1-PP).<ref name="pmid1681447">{{cite journal | vauthors = Blier P, Curet O, Chaput Y, de Montigny C | title = 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 | journal = Neuropharmacology | volume = 30 | issue = 7 | pages = 691–701 | date = July 1991 | pmid = 1681447 | doi = 10.1016/0028-3908(91)90176-C | s2cid = 44297577 }}</ref><ref name="pmid1362206">{{cite journal | vauthors = Miller LG, Thompson ML, Byrnes JJ, Greenblatt DJ, Shemer A | title = Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine | journal = Journal of Clinical Psychopharmacology | volume = 12 | issue = 5 | pages = 341–345 | date = October 1992 | pmid = 1362206 | doi = 10.1097/00004714-199210000-00009 | s2cid = 22449352 }}</ref>
Tandospirone acts as a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[partial agonist]], with a [[dissociation constant|K<sub>i</sub>]] [[affinity (pharmacology)|affinity]] value of 27 ± 5 nM<ref name="pmid1974152">{{cite journal | vauthors = Hamik A, Oksenberg D, Fischette C, Peroutka SJ | title = Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites | journal = Biological Psychiatry | volume = 28 | issue = 2 | pages = 99–109 | date = July 1990 | pmid = 1974152 | doi = 10.1016/0006-3223(90)90627-E | s2cid = 25608914 }}</ref> and approximately 55 to 85% [[intrinsic activity]].<ref name="pmid8745167">{{cite journal | vauthors = Tanaka H, Tatsuno T, Shimizu H, Hirose A, Kumasaka Y, Nakamura M | title = Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain | journal = General Pharmacology | volume = 26 | issue = 8 | pages = 1765–1772 | date = December 1995 | pmid = 8745167 | doi = 10.1016/0306-3623(95)00077-1 }}</ref><ref name="Yabuuchi_2004">{{cite journal | vauthors = Yabuuchi K, Tagashira R, Ohno Y |title=Effects of tandospirone, a novel anxiolytic agent, on human 5-HT<SUB>1A</SUB> receptors expressed in Chinese hamster ovary cells (CHO cells) |journal=Biogenic Amines |year=2004 |volume=18 |issue=3 |pages=319–328 |doi=10.1163/1569391041501933}}</ref> It has relatively weak affinity for the [[5-HT2A receptor|5-HT<sub>2A</sub>]] (1,300 ± 200), [[5-HT2C receptor|5-HT<sub>2C</sub>]] (2,600 ± 60), [[alpha-1 adrenergic|α<sub>1</sub>-adrenergic]] (1,600 ± 80), [[alpha-2 adrenergic|α<sub>2</sub>-adrenergic]] (1,900 ± 400), [[D1 receptor|D<sub>1</sub>]] (41,000 ± 10,000), and [[D2 receptor|D<sub>2</sub>]] (1,700 ± 300) [[receptor (biochemistry)|receptor]]s, and is essentially inactive at the [[5-HT1B receptor|5-HT<sub>1B</sub>]], [[5-HT1D receptor|5-HT<sub>1D</sub>]], [[beta-adrenergic|β-adrenergic]], and [[muscarinic acetylcholine receptor]]s, [[serotonin transporter]], and [[benzodiazepine]] [[allosteric site]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]] (all of which are > 100,000).<ref name="pmid1974152" /> There is evidence of tandospirone having low but significant [[antagonist]]ic activity at the [[alpha-2 adrenergic|α<sub>2</sub>-adrenergic receptor]] through its active [[metabolite]] [[1-(2-pyrimidinyl)piperazine]] (1-PP).<ref name="pmid1681447">{{cite journal | vauthors = Blier P, Curet O, Chaput Y, de Montigny C | title = 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 | journal = Neuropharmacology | volume = 30 | issue = 7 | pages = 691–701 | date = July 1991 | pmid = 1681447 | doi = 10.1016/0028-3908(91)90176-C | s2cid = 44297577 }}</ref><ref name="pmid1362206">{{cite journal | vauthors = Miller LG, Thompson ML, Byrnes JJ, Greenblatt DJ, Shemer A | title = Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine | journal = Journal of Clinical Psychopharmacology | volume = 12 | issue = 5 | pages = 341–345 | date = October 1992 | pmid = 1362206 | doi = 10.1097/00004714-199210000-00009 | s2cid = 22449352 }}</ref>


==Chemistry==
⚫
==Society and culture==


===Name===
===Synthesis===
Tandospirone has also been known as metanopirone.
==Synthesis==
*The [[Noreximide]] [6319-06-8] precursor also has dual uses to make [[Taglutimide]] & [[Tripamide]] & [[Lurasidone]].
*The [[Noreximide]] [6319-06-8] precursor also has dual uses to make [[Taglutimide]] & [[Tripamide]] & [[Lurasidone]].

[[File:Tandospirone synthesis.svg|600px|thumb|center|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-20-0011 Thieme] Synthesis:<ref>{{cite journal |vauthors=((Ishizumi, K.)), ((Kojima, A.)), ((Antoku, F.)) |date=1991 |title=Synthesis and Anxiolytic Activity of N-Substituted Cyclic Imides(1R*,2S*,3R*,4S*)-N-(4-(4-(2-Pyrimidinyl)-1-piperazinyl)butyl)-2,3-bicyclo(2.2.1)heptanedicarboximide(Tandospirone) and Related Compounds. |journal=Chemical and Pharmaceutical Bulletin |volume=39 |issue=9 |pages=2288–2300 |doi=10.1248/cpb.39.2288 |pmid=1687114 |issn=0009-2363 |eissn=1347-5223|doi-access=free }}</ref><ref>{{cite journal |vauthors=((Cybulski, J.)), ((Chilmonczyk, Z.)), ((Szelejewski, W.)), ((Wojtasiewicz, K.)), ((Wróbel, J. T.)) |date=1992 |title=An Efficient Synthesis of Buspirone and its Analogues. |journal=Archiv der Pharmazie |volume=325 |issue=5 |pages=313–315 |doi=10.1002/ardp.19923250513 |s2cid=83676454 |issn=0365-6233 |eissn=1521-4184}}</ref><ref>Castaner, J.; Prous, J. Drugs Fut 1986,11(11),949.</ref> Patent:<ref>Kikuo Ishizumi, Fuji Antoku, Yukio Asami, {{Cite patent|EP|0082402}} (1986 to Sumitomo Chemical Company, Limited).</ref> Sino:<ref>张金生 & 李翎, {{Cite patent|CN|101880274A}} (2010 to PKUCare Southwest Synthetic Pharmaceutical Corp., Ltd.)</ref> [[Radiolabelled]]:<ref>{{cite journal | vauthors=((Nishioka, K.)), ((Kanamaru, H.)) | journal=Journal of Labelled Compounds and Radiopharmaceuticals | title=14C-labeling of a novel anxiolytic agent tandospirone | volume=31 | issue=6 | pages=427–436 | date= June 1992 | issn=0362-4803 | doi=10.1002/jlcr.2580310602}}</ref> Mannich reaction method:<ref>John Bondo Hansen & Mikael Søndergaard THOMSEN, {{Cite patent|WO|2012016569}} (to Conrig Pharma ApS).</ref>]]
[[File:Tandospirone synthesis.svg|600px|thumb|center|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-20-0011 Thieme] Synthesis:<ref>{{cite journal |vauthors=((Ishizumi, K.)), ((Kojima, A.)), ((Antoku, F.)) |date=1991 |title=Synthesis and Anxiolytic Activity of N-Substituted Cyclic Imides(1R*,2S*,3R*,4S*)-N-(4-(4-(2-Pyrimidinyl)-1-piperazinyl)butyl)-2,3-bicyclo(2.2.1)heptanedicarboximide(Tandospirone) and Related Compounds. |journal=Chemical and Pharmaceutical Bulletin |volume=39 |issue=9 |pages=2288–2300 |doi=10.1248/cpb.39.2288 |pmid=1687114 |issn=0009-2363 |eissn=1347-5223|doi-access=free }}</ref><ref>{{cite journal |vauthors=((Cybulski, J.)), ((Chilmonczyk, Z.)), ((Szelejewski, W.)), ((Wojtasiewicz, K.)), ((Wróbel, J. T.)) |date=1992 |title=An Efficient Synthesis of Buspirone and its Analogues. |journal=Archiv der Pharmazie |volume=325 |issue=5 |pages=313–315 |doi=10.1002/ardp.19923250513 |s2cid=83676454 |issn=0365-6233 |eissn=1521-4184}}</ref><ref>Castaner, J.; Prous, J. Drugs Fut 1986,11(11),949.</ref> Patent:<ref>Kikuo Ishizumi, Fuji Antoku, Yukio Asami, {{Cite patent|EP|0082402}} (1986 to Sumitomo Chemical Company, Limited).</ref> Sino:<ref>张金生 & 李翎, {{Cite patent|CN|101880274A}} (2010 to PKUCare Southwest Synthetic Pharmaceutical Corp., Ltd.)</ref> [[Radiolabelled]]:<ref>{{cite journal | vauthors=((Nishioka, K.)), ((Kanamaru, H.)) | journal=Journal of Labelled Compounds and Radiopharmaceuticals | title=14C-labeling of a novel anxiolytic agent tandospirone | volume=31 | issue=6 | pages=427–436 | date= June 1992 | issn=0362-4803 | doi=10.1002/jlcr.2580310602}}</ref> Mannich reaction method:<ref>John Bondo Hansen & Mikael Søndergaard THOMSEN, {{Cite patent|WO|2012016569}} (to Conrig Pharma ApS).</ref>]]


The [[catalytic hydrogenation]] of cis-5-Norbornene-exo-2,3-dicarboxylic anhydride [129-64-6] ('''1''') gives Norbornane-2exo,3exo-dicarboxylic Acid-anhydride [14166-28-0] ('''2'''). Reaction with aqueous ammonia leads to Exo-2,3-norbornanedicarboximide [14805-29-9] ('''3'''). Alkylation with 1,4-dibromobutane [110-52-1] ('''4''') gives [https://pubchem.ncbi.nlm.nih.gov/compound/10661911 CID:10661911] ('''5'''). Alkylation of the remaining halogen with 2-(1-Piperazinyl)Pyrimidine [20980-22-7] ('''6''') completed the synthesis of Tandospirone ('''7''').
The [[catalytic hydrogenation]] of cis-5-Norbornene-exo-2,3-dicarboxylic anhydride [129-64-6] ('''1''') gives Norbornane-2exo,3exo-dicarboxylic Acid-anhydride [14166-28-0] ('''2'''). Reaction with aqueous ammonia leads to Exo-2,3-norbornanedicarboximide [14805-29-9] ('''3'''). Alkylation with 1,4-dibromobutane [110-52-1] ('''4''') gives [https://pubchem.ncbi.nlm.nih.gov/compound/10661911 CID:10661911] ('''5'''). Alkylation of the remaining halogen with 2-(1-Piperazinyl)Pyrimidine [20980-22-7] ('''6''') completed the synthesis of Tandospirone ('''7''').


== References ==
==History==
Tandospirone was introduced in [[Japan]] for the treatment of anxiety disorders in 1996.<ref name="BrileyNutt2012">{{cite book | last=Briley | first=M. | last2=Nutt | first2=D. | title=Anxiolytics | publisher=Birkhäuser Basel | series=Milestones in Drug Therapy | year=2012 | isbn=978-3-0348-8470-9 | url=https://books.google.com/books?id=JZW-BwAAQBAJ&pg=PA99 | access-date=2023-10-07 | page=99}}</ref> It was subsequently also introduced in [[China]] in 2004.<ref name="RiedererLauxNagatsuLe2022">{{cite book | last=Riederer | first=P. | last2=Laux | first2=G. | last3=Nagatsu | first3=T. | last4=Le | first4=W. | last5=Riederer | first5=C. | title=NeuroPsychopharmacotherapy | publisher=Springer International Publishing | series=NeuroPsychopharmacotherapy | year=2022 | isbn=978-3-030-62059-2 | url=https://books.google.com/books?id=G1qaEAAAQBAJ&pg=PA2131 | access-date=2023-10-07 | page=2131}}</ref>
⚫
{{Reflist|30em}}

⚫
==Society and culture==

===Name===
Tandospirone is also known as metanopirone and by the developmental code name SM-3997.<ref name="Elks2014">{{cite book | last=Elks | first=J. | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1149 | access-date=2023-10-07 | page=1149}}</ref><ref name="SchweizerischerApotheker-Verein2004">{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum: International Drug Directory | publisher=Medpharm Scientific Publishers | series=Index Nominum: International Drug Directory | year=2004 | isbn=978-3-88763-101-7 | url=https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA1146 | access-date=2023-10-07 | page=1146}}</ref><ref name="MortonHall2012">{{cite book | last=Morton | first=I.K. | last2=Hall | first2=J.M. | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA257 | access-date=2023-10-07 | page=257}}</ref><ref name="MD" /> It is marketed in Japan under the brand name Sediel.<ref name="Elks2014" /><ref name="SchweizerischerApotheker-Verein2004" /><ref name="MortonHall2012" /><ref name="MD" />

==References==
⚫
{{Reflist}}


{{Anxiolytics}}
{{Anxiolytics}}

Revision as of 18:34, 7 October 2023

Tandospirone
Clinical data
Trade namesSediel
Other namesMetanopirone
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolites1-PPTooltip 1-(2-Pyrimidinyl)piperazine
Elimination half-lifeTandospirone: 2–3 hours
1-PPTooltip 1-(2-Pyrimidinyl)piperazine: 3–5 hours
ExcretionUrine (70%; 0.1% as unchanged drug)
Identifiers
  • (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
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.210.461 Edit this at Wikidata
Chemical and physical data
FormulaC21H29N5O2
Molar mass383.496 g·mol−1
3D model (JSmol)
  • O=C1N(C(=O)[C@H]3[C@@H]1[C@@H]2CC[C@H]3C2)CCCCN5CCN(c4ncccn4)CC5
  • 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- checkY
  • Key:CEIJFEGBUDEYSX-FZDBZEDMSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Tandospirone, sold under the brand name Sediel, is an anxiolytic and antidepressant medication used in Japan and China, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone class of drugs and is closely related to other azapirones like buspirone and gepirone.

Tandospirone was introduced for medical use in Japan in 1996[1] and in China in 2004.[2]

Medical uses

Anxiety and depression

Tandospirone is most commonly used as a treatment for anxiety and depressive disorders, such as generalised anxiety disorder and dysthymia respectively.[3] For both indications it usually takes a couple of weeks for therapeutic effects to begin to be seen,[3] although at higher doses more rapid anxiolytic responses have been seen.[4] It has also been used successfully as a treatment for bruxism.[5]

Augmentation for depression

Tandospirone can be used as an effective augmentation,[clarification needed] especially when coupled with fluoxetine or clomipramine.[6]

Other uses

Tandospirone has been tried successfully as an adjunctive treatment for cognitive symptoms[clarification needed] in schizophrenic individuals.[7]

Side effects

Common adverse effects include:[3][1]

  • Dizziness
  • Drowsiness
  • Insomnia
  • Headache
  • Gastrointestinal disorders
  • Dry mouth
  • Negative influence on explicit memory function[3]
  • Nausea[1]

Adverse effects with unknown frequency include:[3]

It is not believed to be addictive but is known to produce mild withdrawal effects (e.g., anorexia) after abrupt discontinuation.[3]

Pharmacology

Pharmacodynamics

Tandospirone acts as a potent and selective 5-HT1A receptor partial agonist, with a Ki affinity value of 27 ± 5 nM[8] and approximately 55 to 85% intrinsic activity.[9][10] It has relatively weak 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).[8] 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).[11][12]

Chemistry

Synthesis

Thieme Synthesis:[13][14][15] Patent:[16] Sino:[17] Radiolabelled:[18] Mannich reaction method:[19]

The catalytic hydrogenation of cis-5-Norbornene-exo-2,3-dicarboxylic anhydride [129-64-6] (1) gives Norbornane-2exo,3exo-dicarboxylic Acid-anhydride [14166-28-0] (2). Reaction with aqueous ammonia leads to Exo-2,3-norbornanedicarboximide [14805-29-9] (3). Alkylation with 1,4-dibromobutane [110-52-1] (4) gives CID:10661911 (5). Alkylation of the remaining halogen with 2-(1-Piperazinyl)Pyrimidine [20980-22-7] (6) completed the synthesis of Tandospirone (7).

History

Tandospirone was introduced in Japan for the treatment of anxiety disorders in 1996.[1] It was subsequently also introduced in China in 2004.[2]

Society and culture

Name

Tandospirone is also known as metanopirone and by the developmental code name SM-3997.[20][21][22][5] It is marketed in Japan under the brand name Sediel.[20][21][22][5]

References

  1. ^ a b c d Briley, M.; Nutt, D. (2012). Anxiolytics. Milestones in Drug Therapy. Birkhäuser Basel. p. 99. ISBN 978-3-0348-8470-9. Retrieved 2023-10-07.
  2. ^ a b Riederer, P.; Laux, G.; Nagatsu, T.; Le, W.; Riederer, C. (2022). NeuroPsychopharmacotherapy. NeuroPsychopharmacotherapy. Springer International Publishing. p. 2131. ISBN 978-3-030-62059-2. Retrieved 2023-10-07.
  3. ^ a b c d e f Barradell LB, Fitton A (February 1996). "Tandospirone". CNS Drugs. 5 (2): 147–153. doi:10.2165/00023210-199605020-00006.
  4. ^ Nishitsuji K, To H, Murakami Y, Kodama K, Kobayashi D, Yamada T, et al. (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): 121–126. doi:10.2165/00044011-200424020-00007. PMID 17516698. S2CID 38339009.
  5. ^ a b c Tandospirone. The Royal Pharmaceutical Society of Great Britain. 23 September 2011. Retrieved 14 November 2013. {{cite book}}: |work= ignored (help)
  6. ^ Huang X, Yang J, Yang S, Cao S, Qin D, Zhou Y, et al. (November 2017). "Role of tandospirone, a 5-HT1A receptor partial agonist, in the treatment of central nervous system disorders and the underlying mechanisms". Oncotarget. 8 (60). Impact Journals, LLC: 102705–102720. doi:10.18632/oncotarget.22170. PMC 5731992. PMID 29254282.
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  8. ^ a b Hamik A, Oksenberg D, Fischette C, Peroutka SJ (July 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. S2CID 25608914.
  9. ^ Tanaka H, Tatsuno T, Shimizu H, Hirose A, Kumasaka Y, Nakamura M (December 1995). "Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain". General Pharmacology. 26 (8): 1765–1772. doi:10.1016/0306-3623(95)00077-1. PMID 8745167.
  10. ^ Yabuuchi K, Tagashira R, Ohno Y (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): 319–328. doi:10.1163/1569391041501933.
  11. ^ Blier P, Curet O, Chaput Y, de Montigny C (July 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. S2CID 44297577.
  12. ^ Miller LG, Thompson ML, Byrnes JJ, Greenblatt DJ, Shemer A (October 1992). "Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine". Journal of Clinical Psychopharmacology. 12 (5): 341–345. doi:10.1097/00004714-199210000-00009. PMID 1362206. S2CID 22449352.
  13. ^ Ishizumi, K., Kojima, A., Antoku, F. (1991). "Synthesis and Anxiolytic Activity of N-Substituted Cyclic Imides(1R*,2S*,3R*,4S*)-N-(4-(4-(2-Pyrimidinyl)-1-piperazinyl)butyl)-2,3-bicyclo(2.2.1)heptanedicarboximide(Tandospirone) and Related Compounds". Chemical and Pharmaceutical Bulletin. 39 (9): 2288–2300. doi:10.1248/cpb.39.2288. eISSN 1347-5223. ISSN 0009-2363. PMID 1687114.
  14. ^ Cybulski, J., Chilmonczyk, Z., Szelejewski, W., Wojtasiewicz, K., Wróbel, J. T. (1992). "An Efficient Synthesis of Buspirone and its Analogues". Archiv der Pharmazie. 325 (5): 313–315. doi:10.1002/ardp.19923250513. eISSN 1521-4184. ISSN 0365-6233. S2CID 83676454.
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  19. ^ John Bondo Hansen & Mikael Søndergaard THOMSEN, WO 2012016569  (to Conrig Pharma ApS).
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  21. ^ a b Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 1146. ISBN 978-3-88763-101-7. Retrieved 2023-10-07.
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