Description

Levosulpride is an atypical antipsychotic and prokinetic medication. It is the levorotatory enantiomer of sulpiride, meaning it is a mirror image of the sulpiride molecule. Levosulpride is a substituted benzamide and is known for its dual action on both the central nervous system and the gastrointestinal system, making it a versatile drug for a variety of conditions. It is not available in the United States or the United Kingdom, but it is marketed in many other countries, including those in Europe, Asia, and Latin America.

Indications

Levosulpride has a range of indications that vary by country, with its primary uses falling into two main categories: psychiatric disorders and gastrointestinal disorders.

• Gastrointestinal Conditions:
  • Functional Dyspepsia: It is widely used to treat symptoms of indigestion, such as bloating, belching, and nausea, particularly when accompanied by delayed gastric emptying.

• • Gastroesophageal Reflux Disease (GERD): It helps reduce symptoms like heartburn and acid reflux.

• • Irritable Bowel Syndrome (IBS): It is used to manage symptoms like abdominal pain and bloating by improving gut motility.

• Psychiatric Conditions:
  • Schizophrenia: It is used to treat both acute and chronic forms of schizophrenia.

• • Depression: It can be used as a treatment for depression, sometimes in combination with other medications.

• • Anxiety Disorders: It has anxiolytic (anti-anxiety) effects.
• Other Conditions:
  • Vertigo: It is used to treat symptoms of dizziness.

• • Premature Ejaculation: It has been explored as a treatment for this condition due to its effects on the central nervous system.

Mechanism of Action

The mechanism of action of levosulpride is primarily based on its ability to selectively block dopamine D2 receptors, but it also has other effects that contribute to its therapeutic profile. Its action is dose-dependent and location-specific.

1. Dopamine D2 Receptor Antagonism: Levosulpride is a selective antagonist of dopamine D2 receptors. It works by blocking these receptors, which are found in both the brain and the peripheral nervous system, including the gut.

• • Psychiatric Effect: In the brain’s mesolimbic pathway, the blockade of D2 receptors helps to reduce excessive dopaminergic activity, which is thought to be the cause of psychotic symptoms like delusions and hallucinations.

• • Prokinetic Effect: In the gastrointestinal tract, dopamine D2 receptors normally inhibit the release of acetylcholine, a neurotransmitter that promotes muscle contractions. By blocking these D2 receptors, levosulpride removes this inhibition, leading to an increase in acetylcholine release. The elevated acetylcholine levels enhance the strength and frequency of contractions in the stomach and intestines, improving gastrointestinal motility and relieving symptoms of indigestion and reflux.

2. Serotonin 5-HT4 Receptor Agonism: Some research suggests that levosulpride may also act as a moderate agonist at serotonin 5-HT4 receptors. This action would further contribute to its prokinetic effects, as 5-HT4 receptor stimulation also promotes gastrointestinal motility.