Description
Sediel was launched in Japan as an anxiolytic agent and is a member of the
azapirone family. Ready access to the compound is attained from the ex0 Diels-
Alder adduct of maleic anhydride and cyclopentadiene in a four step convergent
approach. Biochemically, it is a partial agonist of the post-synaptic 5-HT1a receptor.
This metabotropic receptor is coupled to the G proteins and suppresses adenylate
cyclase and phosphatidylinositol metabolism systems. It has low affinity for
dopamine D2, 5-HT2 and α1-adreneric receptors and no affinity for benzodiazepine,
GABA or 5-HT1b binding sites. The primary metabolic product is two orders of
magnitude less active. Tandospirone is as effective as benzodiazepines in anxiolytic
activity but does not have the side-effects (low abuse potential, weak sedative, no
anticonvulsant activity).
Originator
Sumitomo (Japan)
Uses
Tandospirone is a 5HT1A receptor partial agonist. Studies indicate that tandospirone significantly reduces haloperidol-induced bradykinesia in a dose dependent manner. The potency of Tandospirone is equal to that of buspirone and approximate one-half that of diazepam. The potency of Tandospirone at dopamine antagonistic action is less than 1/4 that of buspirone.
Definition
ChEBI: 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+).
Preparation
Tandospirone is attained from the exo diels-alder adduct of maleic anhydride and cyclopentadiene in a four step convergent approach.
Biological Activity
5-HT 1A receptor partial agonist (K i = 27 nM) that displays selectivity over 5-HT 2 , 5-HT 1C , α 1 , α 2 , D 1 and D 2 receptors (K i values ranging from 1300-41000 nM). Inactive at 5-HT uptake sites, 5-HT 1B , β -adrenergic, muscarinic and benzodiazepine receptors. Displays anxiolytic activity.
References
[1] shimizu h1, hirose a, tatsuno t, nakamura m, katsube j. pharmacological properties of sm-3997: a new anxioselective anxiolytic candidate. jpn j pharmacol. 1987 dec; 45(4):493-500.
