Tandospirone

Tandospirone

Clinical data
Trade names	Sediel
Other names	Metanopirone
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolites	1-PP
Elimination half-life	Tandospirone: 2–3 hours 1-PP: 3–5 hours
Excretion	Urine (70%; 0.1% as unchanged drug)
Identifiers
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
CAS Number	87760-53-0 N
PubChem CID	91273
IUPHAR/BPS	55
ChemSpider	82421 Y
UNII	190230I669
ChEBI	CHEBI:145673
ChEMBL	ChEMBL274047 Y
CompTox Dashboard (EPA)	DTXSID6048836
ECHA InfoCard	100.210.461
Chemical and physical data
Formula	C21H29N5O2
Molar mass	383.496 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1N(C(=O)[C@H]3[C@@H]1[C@@H]2CC[C@H]3C2)CCCCN5CCN(c4ncccn4)CC5
InChI 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- Y Key:CEIJFEGBUDEYSX-FZDBZEDMSA-N Y
NY (what is this?)  (verify)

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.

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. For both indications it usually takes a couple of weeks for therapeutic effects to begin to be seen, although at higher doses more rapid anxiolytic responses have been seen. It has also been used successfully as a treatment for bruxism.

Augmentation for depression

Tandospirone can be used as an effective augmentation, especially when coupled with fluoxetine or clomipramine.

Other uses

Tandospirone has been tried successfully as an adjunctive treatment for cognitive symptoms in schizophrenic individuals.

Side effects

Common adverse effects include:

• Dizziness
• Drowsiness
• Insomnia
• Headache
• Gastrointestinal disorders
• Dry mouth
• Negative influence on explicit memory function

Adverse effects with unknown frequency include:

• 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) after abrupt discontinuation.

Pharmacology

Pharmacodynamics

Tandospirone acts as a potent and selective 5-HT_1A receptor partial agonist, with a K_i affinity value of 27 ± 5 nM and approximately 55 to 85% intrinsic activity. It has relatively weak affinity for the 5-HT_2A (1,300 ± 200), 5-HT_2C (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-HT_1B, 5-HT_1D, β-adrenergic, and muscarinic acetylcholine receptors, serotonin transporter, and benzodiazepine allosteric site of the GABA_A receptor (all of which are > 100,000). 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).

Society and culture

Name

Tandospirone has also been known as metanopirone.

Synthesis

• The Noreximide [6319-06-8] precursor also has dual uses to make Taglutimide & Tripamide & Lurasidone.

Thieme Synthesis: Patent: Sino:Radiolabelled: Mannich reaction method:

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).