Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tandospirone: Difference between pages

{{Short description|Anxiolytic and antidepressant medication}}

| verifiedrevid = 470477293

| width = 250px

| tradename = Sediel

| routes_of_administration = [[Oral administration|Oral]]

| bioavailability =

| metabolism =

| metabolites = {{Abbrlink|1-PP|1-(2-Pyrimidinyl)piperazine}}

| elimination_half-life = Tandospirone: 2–3 hours<br />{{Abbrlink|1-PP|1-(2-Pyrimidinyl)piperazine}}: 3–5 hours

| excretion = Urine (70%; 0.1% as unchanged drug)

| CAS_number = 87760-53-0

| ATC_suffix =

| ChEBI = 145673

| synonyms = Metanopirone

| SMILES = O=C1N(C(=O)[C@H]3[C@@H]1[C@@H]2CC[C@H]3C2)CCCCN5CCN(c4ncccn4)CC5

'''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==

===Anxiety and depression===

Tandospirone is most commonly used as a treatment for [[anxiety]] and [[depressive disorder]]s, such as [[generalised anxiety disorder]] and [[dysthymia]] respectively.<ref name = CNS/> For both indications it usually takes a couple of weeks for therapeutic effects to begin to be seen,<ref name = CNS>{{cite journal | vauthors = Barradell LB, Fitton A |title=Tandospirone|journal=CNS Drugs|volume=5|issue=2|date=February 1996|pages=147–153|doi=10.2165/00023210-199605020-00006 }}</ref> although at higher doses more rapid anxiolytic responses have been seen.<ref name="pmid17516698">{{cite journal | vauthors = Nishitsuji K, To H, Murakami Y, Kodama K, Kobayashi D, Yamada T, Kubo C, Mine K | display-authors = 6 | title = Tandospirone in the treatment of generalised anxiety disorder and mixed anxiety-depression : results of a comparatively high dosage trial | journal = Clinical Drug Investigation | volume = 24 | issue = 2 | pages = 121–126 | year = 2004 | pmid = 17516698 | doi = 10.2165/00044011-200424020-00007 | s2cid = 38339009 }}</ref> It has also been used successfully as a treatment for [[bruxism]].<ref name = MD>{{cite book| chapter = Tandospirone | title = Martindale: The Complete Drug Reference|publisher=The Royal Pharmaceutical Society of Great Britain|access-date=14 November 2013|date=23 September 2011| chapter-url=http://www.medicinescomplete.com/mc/martindale/current/10442-w.htm}}</ref>

===Augmentation for depression===

Tandospirone can be used as an effective augmentation,{{clarify|date=July 2022}} especially when coupled with [[fluoxetine]] or [[clomipramine]].<ref name="Huang Yang Yang Cao pp. 102705–102720">{{cite journal | vauthors = Huang X, Yang J, Yang S, Cao S, Qin D, Zhou Y, Li X, Ye Y, Wu J | display-authors = 6 | title = Role of tandospirone, a 5-HT1A receptor partial agonist, in the treatment of central nervous system disorders and the underlying mechanisms | journal = Oncotarget | volume = 8 | issue = 60 | pages = 102705–102720 | date = November 2017 | pmid = 29254282 | pmc = 5731992 | doi = 10.18632/oncotarget.22170 | publisher = Impact Journals, LLC }}</ref>

===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>

==Side effects==

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

* Dizziness

* Drowsiness

* Insomnia

* Headache

* Gastrointestinal disorders

* Dry mouth

* Negative influence on explicit memory function<ref name = CNS/>

* Nausea<ref name="BrileyNutt2012" />

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

* [[Hypotension]] (low blood pressure)

* [[Dysphoria]]

* [[Tachycardia]]

* [[Malaise]]

* [[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/>

==Pharmacology==

===Pharmacodynamics===

Tandospirone acts as a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[5-HT1A receptor|5-HT_1A receptor]] [[partial agonist]], with a [[dissociation constant|K_i]] [[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 | doi-access = free }}</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_2A]] (1,300 ± 200), [[5-HT2C receptor|5-HT_2C]] (2,600 ± 60), [[alpha-1 adrenergic|α₁-adrenergic]] (1,600 ± 80), [[alpha-2 adrenergic|α₂-adrenergic]] (1,900 ± 400), [[D1 receptor|D₁]] (41,000 ± 10,000), and [[D2 receptor|D₂]] (1,700 ± 300) [[receptor (biochemistry)|receptor]]s, and is essentially inactive at the [[5-HT1B receptor|5-HT_1B]], [[5-HT1D receptor|5-HT_1D]], [[beta-adrenergic|β-adrenergic]], and [[muscarinic acetylcholine receptor]]s, [[serotonin transporter]], and [[benzodiazepine]] [[allosteric site]] of the [[GABAA receptor|GABA_A 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|α₂-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==

===Synthesis===

*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 | 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 & Pharmaceutical Bulletin | volume = 39 | issue = 9 | pages = 2288–2300 | date = September 1991 | pmid = 1687114 | doi = 10.1248/cpb.39.2288 | doi-access = free | eissn = 1347-5223 }}</ref><ref>{{cite journal |vauthors= Cybulski J, Chilmonczyk Z, Szelejewski W, Wojtasiewicz K, Wróbel JT |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>{{cite journal | vauthors = Prous J, Castaner J| title = SM-3997 | journal = Drugs of the Future| date = 1986 | volume = 11 |issue = 11 | pages = 949 | doi = 10.1358/dof.1986.011.11.53048 }}</ref><ref>{{cite patent | inventor = Ishizumi K, Antoku F, Asami Y | country = EP | number = 0082402 | pubdate = 1986 | assign1 = Sumitomo Chemical Company, Limited) }}</ref><ref>{{cite patent | inventor = Zhang J, Li L | country = CN | number = 101880274A | pubdate = 2010 | assign1 = 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>{{cite patent | inventor = Hansen JB, Thomsen MS | country = WO | number = 2012016569 | assign1 = 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''').

==History==

Tandospirone was introduced in [[Japan]] for the treatment of anxiety disorders in 1996.<ref name="BrileyNutt2012">{{cite book | vauthors = Levine LR, Potter WZ | chapter = The 5-HT1A receptor: an unkept promise | veditors = Briley M, Nutt D | title=Anxiolytics | publisher=Birkhäuser Basel | series=Milestones in Drug Therapy | year=2012 | isbn=978-3-0348-8470-9 | chapter-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 | vauthors = Riederer P, Laux G, Nagatsu T, Le W, Riederer C | title=NeuroPsychopharmacotherapy | publisher=Springer International Publishing | 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>

==Society and culture==

===Name===

Tandospirone is also known as metanopirone and by the developmental code name SM-3997.<ref name="Elks2014">{{cite book | vauthors = Elks 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 | 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 | vauthors = Morton IK, Hall JM | 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}}

{{Antidepressants}}

{{Adrenergic receptor modulators}}

{{Serotonin receptor modulators}}

[[Category:5-HT1A agonists]]

[[Category:Alpha-2 blockers]]

[[Category:Aminopyrimidines]]

[[Category:Antidepressants]]

[[Category:Anxiolytics]]

[[Category:Azapirones]]

[[Category:Cyclopentanes]]

[[Category:Imides]]

[[Category:Piperazines]]