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Tandospirone (SM-3997) is a novel, highly potent and selective 5-HT1A receptor partial agonist with Ki of 27 nM, and exhibits selectivity over SR-2, SR-1C, α1, α2, D1 and D2 receptors (Kis ranging from 1300-41000 nM). It has the potential to be used for treating the central nervous system disorders and the underlying mechanisms.
Physicochemical Properties
| Molecular Formula | C₂₁H₂₉N₅O₂ |
| Molecular Weight | 383.49 |
| Exact Mass | 383.232 |
| CAS # | 87760-53-0 |
| Related CAS # | Tandospirone citrate; 112457-95-1; Tandospirone hydrochloride; 99095-10-0 |
| PubChem CID | 91273 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 613.9±65.0 °C at 760 mmHg |
| Melting Point | 112-113.5° |
| Flash Point | 325.1±34.3 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.589 |
| LogP | 2.02 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 28 |
| Complexity | 572 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | C1C[C@H]2C[C@@H]1[C@H]3[C@@H]2C(=O)N(C3=O)CCCCN4CCN(CC4)C5=NC=CC=N5 |
| InChi Key | CEIJFEGBUDEYSX-FZDBZEDMSA-N |
| InChi Code | 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- |
| Chemical Name | (1R,2S,6R,7S)-4-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-4-azatricyclo[5.2.1.02,6]decane-3,5-dione |
| Synonyms | SM-3997; SM3997; SM 3997; Tandospirone |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | 5-HT1A Receptor ( Ki = 27 nM ) |
| ln Vitro |
Tandospirone is roughly two to three orders of magnitude less potent than 5-HT1A at 5-HT2, 5-HT1C, α1-adrenergic, α2-adrenergic, and dopamine D1 and D2 receptors (Ki values ranging from 1300 to 41000 nM)[1]. Tandospirone is essentially inactive at beta-adrenergic, muscarinic cholinergic, 5-HT uptake sites, 5-HT1B receptors, and benzodiazepine receptors. Tandospirone inhibits protein kinase A (PKA)-mediated protein phosphorylation and neuronal activity by activating postsynaptic 5-HT1A receptor coupled with G-protein (Gi/o)[1]. |
| ln Vivo |
Tandospirone (10-80 mg/kg; i.p.) inhibits freezing behavior in the rat model of conditioned fear stress-induced freezing behavior[3]. Tandospirone hows the anxiolytic effect dependent on the plasma concentration of at 0.5 hours but not 4 hours[3]. |
| Animal Protocol |
Seven-week-old male Sprague-Dawley rats (260-300 g), conditioned fear stress-induced freezing behavior rat model 10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg Intraperitoneal injection |
| References |
[1]. Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites. Biol Psychiatry. 1990 Jul 15;28(2):99-109. [2]. Role of tandospirone, a 5-HT1A receptor partial agonist, in the treatment of central nervous system disorders and the underlying mechanisms. Oncotarget. 2017 Nov 24; 8(60): 102705–102720. [3]. KThe pharmacokinetics and pharmacodynamics of tandospirone in rats exposed to conditioned fear stress. Eur Neuropsychopharmacol. 2006 Jul;16(5):376-82. |
| Additional Infomation |
Tandospirone is a dicarboximide that is (3aR,4S,7R,7aS)-hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione which is substituted by a 4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl group at position 2. It is a potent and selective 5-HT1A receptor partial agonist (Ki = 27 nM). It has a role as an antidepressant and an anxiolytic drug. It is a N-alkylpiperazine, a N-arylpiperazine, a member of pyrimidines, a bridged compound and a dicarboximide. It is a conjugate base of a tandospirone(1+). Tandospirone has been used in trials studying the treatment of Schizophrenia. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 16.7~26 mg/mL (43.5~67.8 mM) Ethanol: ~15 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6076 mL | 13.0381 mL | 26.0763 mL | |
| 5 mM | 0.5215 mL | 2.6076 mL | 5.2153 mL | |
| 10 mM | 0.2608 mL | 1.3038 mL | 2.6076 mL |