Tandospirone (brand name Sediel) is an
anxiolytic
An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...
and
antidepressant drug used in
China and
Japan, where it is marketed by
Dainippon Sumitomo Pharma. It is a member of the
azapirone
Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
Medical uses
Azapirones have shown ...
class of drugs and is closely related to other azapirones like
buspirone
Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to fo ...
and
gepirone
Gepirone is an antidepressant and anxiolytic drug of the azapirone group that was synthesized by Bristol-Myers Squibb in 1986 and has been under development for the treatment of depression but has yet to be marketed. It has been under developmen ...
.
Medical uses
Anxiety and depression
Tandospirone is most commonly used as a treatment for
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
and
depressive disorder
A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the ''Diagnostic and Stat ...
s, such as
generalised anxiety disorder
Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...
and
dysthymia
Dysthymia ( ), also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with lo ...
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
Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used for the treatment of obsessive–compulsive disorder, panic disorder, major depressive disorder, and chronic pain. It may increase th ...
.
Other uses
Tandospirone has been tried successfully as an adjunctive treatment for cognitive symptoms in schizophrenic
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdr ...
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
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
(low blood pressure)
* Dysphoria
Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation.
In psychiatry
Intense states of distress and uneas ...
* Tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
* Malaise
* Psychomotor impairment
It is not believed to be addictive but is known to produce mild withdrawal effects (e.g., anorexia
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
) after abrupt discontinuation.[
]
Pharmacology
Pharmacodynamics
Tandospirone acts as a potent and selective 5-HT1A receptor partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...
, with a Ki affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Par ...
value of 27 ± 5 nM and approximately 55 to 85% intrinsic activity
Intrinsic activity (IA) and efficacy refer to the relative ability of a drug- receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its mol ...
. It has relatively weak affinity for the 5-HT2A (1,300 ± 200), 5-HT2C (2,600 ± 60), α1-adrenergic (1,600 ± 80), α2-adrenergic (1,900 ± 400), D1 (41,000 ± 10,000), and D2 (1,700 ± 300) receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
s, and is essentially inactive at the 5-HT1B, 5-HT1D, β-adrenergic
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
, and muscarinic acetylcholine receptor
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...
s, serotonin transporter
The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...
, and benzodiazepine allosteric site
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
The site to which the effector binds is termed the ''allosteric site ...
of the GABAA 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-(2-Pyrimidinyl)piperazine (1-PP, 1-PmP) is a chemical compound and piperazine derivative. It is known to act as an antagonist of the α2-adrenergic receptor (Ki = 7.3–40 nM) and, to a much lesser extent, as a partial agonist of the 5- ...
(1-PP).
Society and culture
Name
Tandospirone has also been known as metanopirone.
Synthesis
*The Noreximide 319-06-8precursor also has dual uses to make Taglutimide & Tripamide & Lurasidone
Lurasidone, sold under the trade name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.
Common side effects include sleepiness, movement disorders, nausea, and diarrhea. ...
.
The catalytic hydrogenation
Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...
of cis-5-Norbornene-exo-2,3-dicarboxylic anhydride 29-64-6(1) gives Norbornane-2exo,3exo-dicarboxylic Acid-anhydride 4166-28-0(2). Reaction with aqueous ammonia leads to Exo-2,3-norbornanedicarboximide 4805-29-9(3). Alkylation with 1,4-dibromobutane 10-52-1(4) give
CID:10661911
(5). Alkylation of the remaining halogen with 2-(1-Piperazinyl)Pyrimidine 0980-22-7(6) completed the synthesis of Tandospirone (7).
References
{{Serotonin receptor modulators
5-HT1A agonists
Alpha-2 blockers
Aminopyrimidines
Antidepressants
Anxiolytics
Azapirones
Cyclopentanes
Imides
Piperazines