Nemonapride****, also previously known as emonapride and sold under the brand name Emilace, is an atypical antipsychotic which is used in the treatment of schizophrenia. It is taken by mouth. Side effects of nemonapride include akathisia, dystonia, hypokinesia, tremor, hypersalivation, and hyperprolactinemia, among others. The drug acts as a dopamine D2, D3, and D4 receptor antagonist. To a lesser extent, it is also a serotonin 5-HT1A receptor partial agonist. Structurally, nemonapride is a benzamide derivative and is related to sulpiride 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 and China.

Medical uses

Nemonapride is used in the treatment of schizophrenia. It is described as being effective in treating the positive symptoms of schizophrenia. It is also said to have some antidepressant and anxiolytic 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 tablets.

Side effects

Side effects of nemonapride include akathisia, dystonia, hypokinesia, tremor, hypersalivation, and hyperprolactinemia, among others.

Pharmacology

Pharmacodynamics

Nemonapride has been described both as a typical antipsychotic and as an atypical antipsychotic. It is a potent and selective dopamine D2, D3, and D4 receptor antagonist. Its affinities (Ki) 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 effects of nemonapride. In addition to the dopamine D2-like receptors, nemonapride has weaker affinity for the serotonin 5-HT1A and 5-HT2A receptors. Its affinities (Ki) for these receptors are 1.8nM for the serotonin 5-HT1A receptor (11-fold lower than for the D2 receptor) and 9.4nM for the serotonin 5-HT2A receptor (59-fold lower than for the D2 receptor). It is a partial agonist of the serotonin 5-HT1A receptor. It has very weak affinity for sigma receptors (Ki = 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, and cholinergic receptors. In animals, nemonapride suppresses conditioned avoidance responses, inhibits methamphetamine- and apomorphine-induced hyperactivity and stereotypy, produces catalepsy, and has slight central depressant effects.

Pharmacokinetics

Nemonapride is metabolized primarily by the cytochrome P450 enzyme CYP3A4. Its elimination half-life is 2.3 to 4.5hours.

Chemistry

Nemonapride is a benzamide derivative and is structurally related to other dopamine antagonists of the benzamide group such as sulpiride.

Structure and stereochemistry

Nemonapride is a cis-2-methyl-3-amino-pyrrolidine derivative, which was later shown to express most of its action as a drug to treat schizophrenia from its homochiral (+)-(2R,3R) form.

History

Nemonapride was developed by scientists at Yamanouchi Pharmaceuticals via structural modification of the benzamide antiemetic and gastroprokinetic agent metoclopramide. It was first described in the scientific literature by 1980. The name nemonapride was first used by 1989 and this name was designated as its INN 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 INN and JAN. 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 (JP: エミレース) in Japan and China.

Availability

Nemonapride is marketed only in Japan and China. It was also under development for use in other countries, such as France, 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 Kingdom, or Europe.