Amisulpride
Encyclopedia
Amisulpride is an atypical antipsychotic
used to treat psychosis
in schizophrenia
and episodes of mania
in bipolar disorder
. In small doses it is also used to treat depression. It was introduced by Sanofi-Aventis
in the 1990s.
. It has high affinity for these receptors with dissociation constant
s of 2.8 nM and 3.2 nM, respectively. Although standard doses in the 400 to 1200 mg a day range used to treat psychosis
inhibit dopaminergic
neurotransmission
, low doses in the 50 to 200 mg range preferentially block inhibitory pre-synaptic autoreceptor
s. This results in a facilitation of dopamine activity, and for this reason, low dose amisulpride has also been used to treat clinical depression
.
Amisulpride and its relative sulpiride
have been shown to bind to and activate the GHB receptor
at doses that are used for therapeutic purposes. Activation of the GHB receptor is known to inhibit the release of dopamine
and even appears to have neuroleptic effects itself . For this reason it is believed that amisulpride and sulpiride's action at this receptor may contribute to their efficacy in treating psychosis.
Though it has long been widely assumed that dopaminergic modulation is solely responsible for the respective antidepressant
and antipsychotic
properties of amisulpride, it has recently been shown that it also acts as a potent antagonist at the 5-HT7 receptor
. Several of the other atypical antipsychotics such as risperidone
and ziprasidone
are potent antagonists at the 5-HT7 receptor as well, and selective antagonists of the receptor show antidepressant properties themselves. To characterize the role of the 5-HT7 receptor in the antidepressant effects of amisulpride, a study prepared 5-HT7 receptor knockout mice. The study found that in two widely used rodent models of depression, the tail suspension test, and the forced swim test, those mice did not exhibit an antidepressant response upon treatment with amisulpride. These results indicate that 5-HT7 receptor antagonism plays a major role in the antidepressant effects of amisulpride.
for use in the United States
, but it is used in Europe (France
, Germany
, Italy
, Switzerland
, Russia
, United Kingdom
, etc.) and Australia
to treat psychoses
and schizophrenia
. In Italy, in 50 mg doses, it is also used as a treatment for dysthymia (under the brand name Deniban).
and equal to :
In another study, anxiety measured by HAM-A total mean score decreased significantly more with amisulpride 50 mg/day (63%) than with fluoxetine
(Prozac)20 mg/day (54%; P = 0.021). Another recent study concludes that amisulpride is an appropriate first-line treatment for the management of acute psychosis.
induction, thereby causing amenorrhoea
and galactorrhoea in women, nausea
, weight gain
, insomnia
, akathisia
, sexual dysfunction
, although much less than similar drugs in its class, and less commonly QT interval
prolongation (which can lead to serious heart arrhythmias). Overdoses of amisulpride have been linked with torsades de pointes
.
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
used to treat psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
in schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and episodes of mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
in bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
. In small doses it is also used to treat depression. It was introduced by Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
in the 1990s.
Pharmacology
Amisulpride functions primarily as a D2 and D3 receptor antagonistReceptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
. It has high affinity for these receptors with dissociation constant
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...
s of 2.8 nM and 3.2 nM, respectively. Although standard doses in the 400 to 1200 mg a day range used to treat psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
inhibit dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
, low doses in the 50 to 200 mg range preferentially block inhibitory pre-synaptic autoreceptor
Autoreceptor
An autoreceptor is a receptor located on presynaptic nerve cell membranes and serves as a part of a feedback loop in signal transduction. It is sensitive only to those neurotransmitters or hormones that are released by the neuron in whose membrane the autoreceptor sits.Canonically, a presynaptic...
s. This results in a facilitation of dopamine activity, and for this reason, low dose amisulpride has also been used to treat clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
.
Amisulpride and its relative sulpiride
Sulpiride
Sulpiride is an...
have been shown to bind to and activate the GHB receptor
GHB receptor
Gamma-hydroxybutyrate receptor or GHB receptor , originally identified as GPR172A, is a G protein-coupled receptor that binds gamma-Hydroxybutyric acid .-History:...
at doses that are used for therapeutic purposes. Activation of the GHB receptor is known to inhibit the release of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and even appears to have neuroleptic effects itself . For this reason it is believed that amisulpride and sulpiride's action at this receptor may contribute to their efficacy in treating psychosis.
Though it has long been widely assumed that dopaminergic modulation is solely responsible for the respective 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;...
and antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
properties of amisulpride, it has recently been shown that it also acts as a potent antagonist at the 5-HT7 receptor
5-HT7 receptor
The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin The 5-HT7 receptor is coupled to Gs and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various...
. Several of the other atypical antipsychotics such as risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
and ziprasidone
Ziprasidone
Ziprasidone was the fifth atypical antipsychotic to gain FDA approval . In the United States, Ziprasidone is Food and Drug Administration approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients...
are potent antagonists at the 5-HT7 receptor as well, and selective antagonists of the receptor show antidepressant properties themselves. To characterize the role of the 5-HT7 receptor in the antidepressant effects of amisulpride, a study prepared 5-HT7 receptor knockout mice. The study found that in two widely used rodent models of depression, the tail suspension test, and the forced swim test, those mice did not exhibit an antidepressant response upon treatment with amisulpride. These results indicate that 5-HT7 receptor antagonism plays a major role in the antidepressant effects of amisulpride.
Availability
Amisulpride is not approved by the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
for use in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, but it is used in Europe (France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
, Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
, Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
, Switzerland
Switzerland
Switzerland name of one of the Swiss cantons. ; ; ; or ), in its full name the Swiss Confederation , is a federal republic consisting of 26 cantons, with Bern as the seat of the federal authorities. The country is situated in Western Europe,Or Central Europe depending on the definition....
, Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
, United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, etc.) and Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
to treat psychoses
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. In Italy, in 50 mg doses, it is also used as a treatment for dysthymia (under the brand name Deniban).
Efficacy as an antidepressant
As an antidepressant, amisulpride is significantly more effective than :- SertralineSertralineSertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
(Zoloft) - ImipramineImipramineImipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...
(Tofranil)
and equal to :
- AmitriptylineAmitriptylineAmitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...
(Elavil, Endep) - AmineptineAmineptineAmineptine was developed by the French Society of Medical research in the 1960s. Under the trade-names is used as an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting...
In another study, anxiety measured by HAM-A total mean score decreased significantly more with amisulpride 50 mg/day (63%) than with fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
(Prozac)20 mg/day (54%; P = 0.021). Another recent study concludes that amisulpride is an appropriate first-line treatment for the management of acute psychosis.
Side effects
ProlactinProlactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
induction, thereby causing amenorrhoea
Amenorrhoea
Amenorrhoea , amenorrhea , or amenorrhœa, is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen during pregnancy and lactation , the latter also forming the basis of a form of contraception known as the lactational amenorrhoea method...
and galactorrhoea in women, nausea
Nausea
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...
, weight gain
Weight gain
Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...
, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
, sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
, although much less than similar drugs in its class, and less commonly QT interval
QT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
prolongation (which can lead to serious heart arrhythmias). Overdoses of amisulpride have been linked with torsades de pointes
Torsades de pointes
Torsades de pointes, or simply torsades, is a French term that literally means "twisting of the points". It was first described by Dessertenne in 1966 and refers to a specific, rare variety of ventricular tachycardia that exhibits distinct characteristics on the electrocardiogram .- Presentation...
.