Tandospirone

Tandospirone

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 of administration	Oral
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 Y
UNII	190230I669 Y
ChEMBL	CHEMBL274047 Y
Chemical data
Formula	C21H29N5O2
Molecular mass	383.487 g/mol
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 (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

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 be start being seen, although at higher doses more rapid anxiolytic responses have been seen. It has also been used successfully as a treatment for bruxism.

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

Adverse effects

Common adverse effects include:

• Dizziness
• Drowsiness
• Insomnia
• Headache
• Gastrointestinal disorders
• Dry mouth

Adverse effects with unknown frequency include:

• Hypotension (low blood pressure)
• Dysphoria
• Tachycardia
• Malaise
• Psychomotor impairment

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

Chemistry

Pharmacology

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 55-85% intrinsic activity. It has weak and clinically negligible 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 (SERT), and benzodiazepine (BDZ) 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), however.

See also

• Buspirone
• Gepirone
• Eptapirone