Tandospirone, sold under the brand name Sediel, is an

anxiolytic An anxiolytic (; also antipanic or anti-anxiety 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 anxie ...

and

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used in

Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...

and

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

, where it is marketed by

Dainippon Sumitomo Pharma is a Japanese multinational pharmaceutical company. The company is focused on oncology, psychiatry, neurology, women's health issues, urological diseases among other areas. Its headquarters are located in Chuo-ku, Osaka. History The original ...

. It is a member of the

azapirone Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as Augmentation (psychiatry), add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). List of ...

class of drugs and is closely related to other azapirones like

buspirone Buspirone, sold under the brand name Buspar among others, is an anxiolytic, a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder (GAD). It is a serotonin 5-HT1A receptor, 5-HT1A receptor partial ag ...

and

gepirone Gepirone, sold under the brand name Exxua, is a medication used for the treatment of major depressive disorder. It is taken orally. Side effects of gepirone include dizziness, nausea, insomnia, abdominal pain, and dyspepsia (indigestion). Ge ...

. Tandospirone was introduced for medical use in Japan in 1996 and in China in 2004.

Medical uses

Anxiety and depression

Tandospirone is most commonly used as a treatment for

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

and

depressive disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental disorder, mental and Abnormal behavior, behavioral Disorder (medicine), disorder where the main underlying characteristic is a disturbance in the per ...

s, such as

generalised anxiety disorder Generalized anxiety disorder (GAD) is an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioning. Individuals with GAD are often overly conc ...

and

dysthymia Dysthymia ( ), known as persistent depressive disorder (PDD) in the DSM-5-TR and dysthymic disorder in ICD-11, is a psychiatric condition marked by symptoms that are similar to those of major depressive disorder, but which persist for at leas ...

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 Bruxism is excessive teeth grinding or jaw clenching. It is an oral Parafunctional habit, parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; the global prevalence of brux ...

Augmentation for depression

Tandospirone can be used as an effective augmentation, especially when coupled with

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyper ...

Other uses

Tandospirone might been tried successfully as an adjunctive treatment for cognitive symptoms in

schizophrenic Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

individuals.

Side effects

Common adverse effects include: * Dizziness * Drowsiness * Insomnia * Headache * Gastrointestinal disorders * Dry mouth * Negative influence on explicit memory function * Nausea Adverse effects with unknown frequency include: *

Hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

(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 In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...

* Psychomotor impairment It is not believed to be addictive but is known to produce mild withdrawal effects (e.g.,

anorexia Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Individuals wit ...

) after abrupt discontinuation.

Pharmacology

Pharmacodynamics

Tandospirone acts as a potent and selective 5-HT_1A receptor

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

, with a K_i

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 Pa ...

value of 27 ± 5 nM and approximately 55 to 85%

intrinsic activity Intrinsic activity (IA) and efficacy (Emax) 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 ...

. 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)

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

s, and is essentially inactive at the 5-HT_1B, 5-HT_1D,

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 bet ...

, and

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

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 t ...

, and

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

allosteric site In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...

of the GABA_A receptor (all of which are > 100,000). There is evidence of tandospirone having low but significant

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.α₂-adrenergic receptor through its active

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

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).

Chemistry

Synthesis

*The Noreximide 319-06-8precursor also has dual uses to make Taglutimide & Tripamide &

Lurasidone Lurasidone, sold under the brand name Latuda among others, is an atypical antipsychotic medication used to treat schizophrenia and bipolar depression. It is taken by mouth. Common side effects include sedation, indigestion, nausea, and inso ...

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 98 may refer to: * 98 (number) * Windows 98, a Microsoft operating system * 98 Ianthe, a main-belt asteroid * Oldsmobile 98, a full-sized luxury car Years * 98 BC * AD 98 * 1998 * 2098 See also * Californium (atomic number), a chemical element * ...

(6) completed the synthesis of Tandospirone (7).

History

Tandospirone was introduced in

for the treatment of anxiety disorders in 1996. It was subsequently also introduced in

in 2004.

Society and culture

Name

Tandospirone is also known as metanopirone and by the developmental code name SM-3997. It is marketed in Japan under the brand name Sediel.

References

{{Serotonin receptor modulators 5-HT1A agonists Alpha-2 blockers Aminopyrimidines Antidepressants Anxiolytics Azapirones Cyclopentanes Imides 1-(2-Pyrimidinyl)piperazines