Nemonapride, also previously known as emonapride and sold under the brand name Emilace, is an

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...

which is used in the treatment of

schizophrenia 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 ...

. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of nemonapride include

akathisia Akathisia (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still. Usually, the legs are most prominently affected. Those a ...

dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...

hypokinesia Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a sy ...

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

hypersalivation Hypersalivation or hypersialosis is the excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva.Medscape > HypersalivationBy Erica Brownfield. P ...

, and

hyperprolactinemia Hyperprolactinaemia (also spelled hyperprolactinemia) is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. ...

, among others. The drug acts as a

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

D₂, D₃, and D₄ receptor

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. To a lesser extent, it is also a

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

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 ...

Structurally A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

, nemonapride is a

benzamide Benzamide is an organic compound with the chemical formula of C7H7NO. It is the simplest amide derivative of benzoic acid. In powdered form, it appears as a white solid, while in crystalline form, it appears as colourless crystals. It is slightly ...

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

and is related to

sulpiride Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic (although some texts have referred to it as a typical antipsychotic) medication of the benzamide class which is used mainly in the treatment of psychosi ...

and other benzamides. Nemonapride was introduced for medical use in either 1991 or 1997. It was developed and marketed by Yamanouchi Pharmaceuticals. The drug is approved only 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 ...

Medical uses

Nemonapride is used in the treatment of

. It is described as being effective in treating the

positive symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

of schizophrenia. It is also said to have some

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 ...

and

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 ...

effects. However, clinical data on nemonapride are described as being somewhat limited.

Available forms

Nemonapride is available in the form of 3 and 10mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

tablets.

Side effects

s of nemonapride include

, and

, among others.

Pharmacology

Pharmacodynamics

Nemonapride has been described both as a

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics m ...

and as an

. It is a potent and selective

D₂, D₃, and D₄ receptor

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. Its affinities (K_i) for these receptors are 0.16nM for the dopamine D₂ receptor, 0.26nM for the dopamine D₃ receptor, and 0.31nM for the dopamine D₄ receptor. Antagonism of the dopamine D₂ receptor is thought to be responsible for the

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

effects of nemonapride. In addition to the dopamine D₂-like receptors, nemonapride has weaker affinity for the

5-HT_1A and 5-HT_2A receptors. Its affinities (K_i) for these receptors are 1.8nM for the serotonin 5-HT_1A receptor (11-fold lower than for the D₂ receptor) and 9.4nM for the serotonin 5-HT_2A receptor (59-fold lower than for the D₂ receptor). It is a

of the serotonin 5-HT_1A receptor. It has very weak affinity for

sigma receptor Sigma receptors (σ-receptors) are protein receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, sigma-1 rec ...

s (K_i = 80–3,000nM) as well. Besides these specific receptors, nemonapride is described as having very weak affinity for the dopamine D₁, serotonin 5-HT₂,

adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...

, and cholinergic receptors. In animals, nemonapride suppresses conditioned avoidance responses, inhibits

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

- and apomorphine-induced

hyperactivity Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...

and

stereotypy A stereotypy (, ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are foun ...

, produces

catalepsy Catalepsy (from Ancient Greek , , "seizing, grasping") is a neurological condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and symptoms Sympt ...

, and has slight central depressant effects.

Pharmacokinetics

Nemonapride is

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

primarily by the

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

. Its

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

is 2.3 to 4.5hours.

Chemistry

Nemonapride is a

and is structurally related to other dopamine antagonists of the benzamide group such as

Structure and stereochemistry

Nemonapride is a ''cis''-2-methyl-3-amino-

pyrrolidine Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most ...

derivative, which was later shown to express most of its action as a drug to treat

from its homochiral (+)-(2R,3R) form.

History

Nemonapride was developed by scientists at Yamanouchi Pharmaceuticals via structural modification of the

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may ...

and

gastroprokinetic agent A prokinetic agent (also prokineticin, gastroprokinetic agent, gastrokinetic agent or propulsive) is a type of drug which enhances gastrointestinal motility by increasing the frequency or strength of contractions, but without disrupting their rhyt ...

metoclopramide Metoclopramide is a medication used to treat nausea, vomiting, gastroparesis, and gastroesophageal reflux disease. It is also used to treat migraine headaches. Common side effects include feeling tired, diarrhea, akathisia, and tardive dyski ...

. It was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

by 1980. The name ''nemonapride'' was first used by 1989 and this name was designated as its in 1991. The drug was launched in May 1991. However, other sources state that it was launched in 1997.

Society and culture

Names

''Nemonapride'' is the generic name of the drug and its and . It was also previously known as ''emonapride'' and by its former developmental code name ''YM 09151-2''. In addition, nemonapride is known by its brand name ''Emilace'' (: エミレース) in

and

Availability

Nemonapride is marketed only in

and

. It was also under development for use in other countries, such as

France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...

, but development in other countries was discontinued. There are no further plans for nemonapride to be developed for use in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

, the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

, or

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

References

{{Serotonin receptor modulators 5-HT1A agonists Atypical antipsychotics Benzamides Chloroarenes D2 antagonists D3 antagonists D4 antagonists Phenol ethers Pyrrolidines