Tandospirone
Encyclopedia
Tandospirone 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
.
and selective
5-HT1A receptor
partial agonist
, with a Ki
affinity value of 27 ± 5 nM and approximately 55-85% intrinsic activity
. It has weak and clinically negligible 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
s, and is essentially inactive at the 5-HT1B
, 5-HT1D
, β-adrenergic, and muscarinic acetylcholine receptor
s, serotonin transporter
(SERT), and benzodiazepine
(BDZ) allosteric site of the GABAA receptor (all of which are > 100,000). There is evidence of tandospirone having low but significant antagonist
ic activity at the α2-adrenergic receptor through its active metabolite
1-(2-pyrimidinyl)piperazine
(1-PP), however.
of 30 mg/daily taken in divided doses of 10 mg three times per day due to its short half-life
. Though originally considered a relatively weak anxiolytic agent, a clinical study found that doubling the dose to 60 mg/daily resulted in a "remarkable anxiolytic effect with an early onset of action
, and without significant adverse effect
s", as well as "excellent anxiolytic efficacy that is comparable to that of the benzodiazepine
s".
, diarrhea
, headache
, dizziness
, and restlessness
.
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
and antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
used in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
and Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, where it is marketed by Dainippon Sumitomo Pharma
Dainippon Sumitomo Pharma
is a pharmaceutical company based in Japan.The original Dainippon Pharmaceuticals was established in 1885 by Nagayo Sensai, a graduate of Tekijuku – the first private medical school in Japan established by Ogata Kōan. It was set up as a wholly private company invested by a number of people in...
. It is a member of the azapirone and piperazine
Piperazine
Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste....
chemical classes and is closely related to other agents like buspirone
Buspirone
Buspirone is an anxiolytic psychoactive drug of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder Bristol-Myers Squibb gained FDA approval of buspirone in 1986 for treatment of GAD...
and gepirone
Gepirone
Gepirone is a psychoactive drug and research chemical of the piperazine and azapirone chemical classes. It is currently under clinical development in an extended release form as an anxiolytic and antidepressant agent...
.
Pharmacology
Tandospirone acts as a potentPotency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
and selective
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...
5-HT1A receptor
5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...
partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
, with a Ki
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...
affinity value of 27 ± 5 nM and approximately 55-85% intrinsic activity
Intrinsic activity
Intrinsic activity or efficacy refers 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 molecular target, and the EC50, which is a measure of the...
. It has weak and clinically negligible affinity for the 5-HT2A
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
(1,300 ± 200), 5-HT2C
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
(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 (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s, and is essentially inactive at the 5-HT1B
5-HT1B receptor
5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.-Tissue distribution and function:...
, 5-HT1D
5-HT1D receptor
5-hydroxytryptamine receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT1D acts on the central nervous system, and affects locomotion and anxiety...
, β-adrenergic, and muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
s, serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
(SERT), and benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
(BDZ) allosteric site of the GABAA receptor (all of which are > 100,000). There is evidence of tandospirone having low but significant antagonist
Antagonist
An antagonist is a character, group of characters, or institution, that represents the opposition against which the protagonist must contend...
ic activity at the α2-adrenergic receptor through its active metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
1-(2-pyrimidinyl)piperazine
1-(2-Pyrimidinyl)piperazine
1-piperazine is a chemical compound and piperazine derivative. It is known to act as an α2-adrenergic receptor antagonist, and as a 5-HT1A receptor partial agonist to a much lesser extent...
(1-PP), however.
Dosage
Tandospirone is typically used at a doseDose (biochemistry)
A dose is a quantity of something that may impact an organism biologically; the greater the quantity, the larger the dose. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement...
of 30 mg/daily taken in divided doses of 10 mg three times per day due to its short half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
. Though originally considered a relatively weak anxiolytic agent, a clinical study found that doubling the dose to 60 mg/daily resulted in a "remarkable anxiolytic effect with an early onset of action
Onset of action
Onset of action is the duration of time it takes for a drug's effects to come to prominence upon administration. With oral administration, it typically ranges anywhere from 20 minutes to over an hour, depending on the drug in question. Other methods of ingestion such as smoking or injection can...
, and without significant adverse effect
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s", as well as "excellent anxiolytic efficacy that is comparable to that of the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s".
Side effects
Side effects of tandospirone and other 5-HT1A partial agonists are relatively mild and may include nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, and restlessness
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
.