Levosulpiride: Uses, Interactions, Mechanism of Action

LEVOSULPIRIDE:

A substituted benzamide antipsychotic called levosulpiride is said to be a selective antagonist. of contral dopamine recoptors. Its chemical name is N-[(2S)-1-Ethypyrrolidin-2-yl]methyl]-2-methoxy-5-sulfamoylbenzamide.

CLINICAL PHARMACOLOGY:

Mechanism Of Action:

Levosuipiride is a selective antagonist at dopamine (D2) receptors. Levosulpiride regulates the dynamics of the digestive system by acting on both the central and peripheral nervous circuits.

The following have an impact on dopamine autoreceptors.

• In contrast to typical antipsychotics, which are 10–20 times more potent at the D2 than the D3 receptor, levosulpiride's affinity for the D2 receptor, a subset of the D2 receptor family that also includes the D3 and D4 receptors, is only 1-2 times greater than that for the D3 receptor.
• As a result of the dopamine autoreceptor's higher affinity for ligands than the dopamine postsynaptic receptor and the D3 ligands' greater preference for autoreceptors, levosulpiride preferentially blocks dopamine autoreceptors on presynaptic neurons at low doses.
• Low-dose levosulpinide increases dopaminergic neurotransmission by increasing presynaptic synthesis and release of dopamine (this is because it blocks the dopamine autoreceptor, which inhibits presynaptic synthesis and release of dopamine).
• Levosulpiride dosages between 50 and 200 mg per day are considered to be low doses. At these dosages, levosulpiride treats depressive and somatoform disorders as well as the negative and cognitive symptoms of schizophrenia.

Action on the dopamine postsynaptic receptors:

• Levosulpiride also binds to D2 dopamine postsynaptic receptors and blocks them at high doses.
• Dopaminergic neurotransmission is consequently reduced.
• High doses of levosulpiride in humans typically refer to daily doses of 400–800 mg. Levosulpiride is effective for treating positive symptoms of schizophrenia at these doses.

Adrenergic receptors are indirectly affected by:

• Beta adrenoceptors in the cortex are downregulated by levosulpiride. This effect could support the medication's antidepressant properties.
• Absence of binding to additional receptors:.
• Since levosulpiride does not obstruct 5-HT2 serotonergic and H1 histaminic receptors, it is.
• It's unlikely to occasionally have negative effects like sedation, increased appetite, or weight gain.
• Levosulpiride doesn't block alpha-1 adrenergic receptors, making postural hypotension unlikely.
• Levosulpiride does not block muscarinic cholinergic receptors, making it unlikely to have side effects like dry mouth, blurred vision, impaired accommodation, constipation, and trouble urinating.

PHAMACOKINETICS:

About 30% of levosulpiride's bioavailability is slowly absorbed from the digestive tract. Plasma proteins only hold less than 40% of levosulpiride. The plasma half-life is about 9.7 hours, and the peak plasma concentration happens after 3 hours. It is primarily eliminated largely unchanged by the kidneys in the urine.

USES:

The oral use of levosupiride tablets is advised:

• The disease of gastroesophageal reflux.
• Irritable bowel syndrome.
• A delayed gastric emptying caused by an organic factor, such as neoplasia or diabetic gastroparalysis, is known as dyspeptic syndrome. ) and to a functional disorder.
• A necessary cephalgia.
• Both a central and/or peripheral source of vertigo.
• reactive as well as endogenous depression.
• Somatic illness.
• Acute and chronic schizophrenia are especially advised for negative symptoms (after disorder).

ADVERSE REACTIONS:

Sedation, hypotension, and precocious dyskinesia are some of the negative effects of levosulpiride that are particularly noticeable in the elderly. The occurrence of psychomotor excitation, autonomic disturbance, allergic reactions, and extrapyramidal effects like tremors and dystonia were all extremely rare. These are all small-scale and reversible effects.

Many disorders, including amenorrhea, gynecomastia, galactorrhoea, hyperprolactinemia, and changes in libido seen in particular cases, are connected to the reversible effects of levosulpiride on the functionality of the hypothalamus-pituitary-gonadal axis, which is similar to that known in many neuroleptic drugs. The presence of ventricular arrhythmias like torsades de pointes, ventricular tachycardia, and ventricular fibrillation arrest is also possible.

CONTRAINDICATIONS:

Levosulpiride should not be used in the following circumstances.

• People with a history of levosulpiride hypersensitivity or hypersensitivity to any other product ingredient.
• In cases of epilepsy, manic illnesses, and manic phases of manic-depressive psychosis.
• People who have malignant mastopathy and a tendency toward hyperprolactineemia.
• Patients with pheochromocytomas, which may lead to a hypertensive crisis due to the release of catecholamine from the tumor.
• In the presence of perforations, mechanical obstruction, or gastrointestinal bleeding.
• Expectant mothers and breastfeeding mothers.
• The child population.

PRECAUTIONS:

Levosulpiride should only be used with caution in the following situations.

Patients taking levosulpiride should be made aware that at higher doses, somnolence, numbness, and dyskinesia may occur; as a result, patients shouldn't operate machinery or drive a car.

> The patient should be closely watched if it is thought to be necessary for re-treatment with antipsychotics.

> Steer clear of using other neuroleptics concurrently in therapy.

> Patients who have heart disease or who have a history of QT protonation in their family should use caution.

> Steer clear of drinking alcohol while driving.

DRUG INTERSACTIONS:

General:

The risk of cardiac arrhythmias increases when neuroleptics and medications that prolong the QT interval are taken together.

Not to be taken concurrently with medications that disturb electrolytes.

Antacids: 

Levosulpiride's mean oral bioavailability may be decreased by taking it concurrently with therapeutic doses of sucralfate or an antacid containing aluminum and magnesium hydroxide.

Anticholinergics, narcotics, or analgesics may be used to lessen the effect that levosulpiride has on gastrointestinal motility.

Psychopharmacological Agents:

The physician must exercise extra caution and vigilance when using one psychopharmacological agent concurrently with another in order to prevent any unanticipated side effects or drug interactions.

OVERDOSAGE:

Extrapyramidal or sleep disturbances have never been reported in internal medicine, but they may eventually happen at very high doses. In this situation, it will be sufficient to stop the therapy or reduce the doses as determined by the doctor.