Melperon

Melperone is a drug from the butyrophenone subgroup and exhibits neuroleptic effects characteristic of them.

The drug blocks the activity of dopamine endings, which leads to a weakening of the intensity of the dopamine neurotransmitter. At the same time, the drug demonstrates a powerful antiserotonergic effect, while the antipsychotic effect develops only with the introduction of large doses of the drug. [ 1 ]

Melperone may lead to the development of antiarrhythmic activity and muscle relaxation. [ 2 ]

Indications Melperon

It is used for the following disorders:

• dysomnia, psychomotor agitation or agitation and confusion in the elderly and people with mental disorders;
• dementia, neuroses or psychoses, as well as oligophrenia associated with organic brain damage.

Release form

The medicinal substance is released in the form of a liquid for oral administration - 5 mg/ml in vials with a volume of 0.2 or 0.3 l. Inside the pack - 1 such vial and a dosing cup.

Pharmacodynamics

Melperone hydrochloride is butyrophen. Its synthesis rate with D2 endings is almost 200 times lower than that of haloperidol. In addition to the dopaminergic effect, the drug also demonstrates a powerful antiserotonergic effect.

After the administration of melperone, affective relaxation is observed, which is tied to the size of the dose of the drug, and has a tendency to reduce drowsiness. Antipsychotic activity against delirium, hallucinations and autism develops only when using large doses of the drug.

In addition to the above-described basic properties, which are characteristic of neuroleptics with a weak effect, the drug has antiarrhythmic and muscle relaxant effects.

Melperone differs from other neuroleptics in that in therapeutic doses it has no effect on the cerebral seizure threshold. A slight increase in this threshold may be observed when using average therapeutic doses of the drug.

The drug's activity in relation to extrapyramidal motor activity is rather weak.

Pharmacokinetics

When administered orally, the drug is fully and rapidly absorbed, undergoing intensive metabolic processes during the first intrahepatic passage.

Plasma level Cmax is observed after 60-90 minutes from the moment of drug administration.

In case of increasing the dosage, a non-linear increase in plasma Cmax values of melperone occurs due to the peculiarities of intrahepatic metabolic processes.

The level of protein synthesis is 50% (18% is synthesized with intraserum albumin).

Food intake does not alter the absorption of the drug or its blood levels.

Melperone is highly metabolized intrahepatically, almost completely; 5-10% of the unchanged active ingredient is excreted through the kidneys. The half-life of a single dose is approximately 4-6 hours. In the case of repeated administration, this value increases to approximately 6-8 hours.

The metabolic processes of the drug are not changed by substances that induce intrahepatic enzymes (phenytoin with phenobarbital and carbamazepine), which distinguishes it from other derivatives of butyrophenone.

Dosing and administration

The dosage is selected taking into account age, personal sensitivity, weight and severity of the disease.

To obtain a mild sedative effect, which is accompanied by an improvement in mood, the medication is used in a daily dose of 20-75 mg.

Persons with confusion and agitation should initially take the drug in a dose of 0.05-0.1 g per day. If necessary, with the doctor's prescription, this dose can be increased to 0.2 g. The maximum permissible daily dosage is 0.4 g.

• Application for children

Not intended for use in persons under 12 years of age.

Use Melperon during pregnancy

Melperone should not be prescribed to pregnant women.

If there is a need to use it during breastfeeding, breastfeeding should be discontinued during the period of therapy.

Contraindications

Among the contraindications:

• severe intolerance to melperone, other butyrophenones or other components of the drug;
• acute poisoning or coma caused by opiates, alcohol, sleeping pills and other psychotropic drugs that weaken the central nervous system (antidepressants with neuroleptics and lithium salts);
• severe liver failure;
• history of CNS.

Side effects Melperon

Main side effects:

• decreased blood pressure, fatigue, reflex increase in heart rate, as well as orthostatic dysregulation;
• signs of shaking palsy (rigidity and tremors), disorders of voluntary movements (extrapyramidal manifestations) and hyperkinesia;
• weakening of bile outflow processes, temporary increase in the activity of liver enzymes and jaundice;
• epidermal signs of allergy;
• thrombocyto-, leuko- or pancytopenia.

Overdose

Drug poisoning can lead to a potentiation of negative symptoms.

Symptomatic actions are performed.

Interactions with other drugs

The use of the drug together with ethyl alcohol causes an increase in the activity of the latter.

Administration in combination with substances that suppress the activity of the central nervous system (including analgesics, antihistamines, sleeping pills and other psychotropic drugs) may provoke an increase in the sedative effect or respiratory depression.

The use of drugs together with tricyclics can provoke a mutual enhancement of drug activity.

Combination with the drug may enhance the activity of antihypertensive drugs.

Use with dopamine antagonists (eg, levodopa) may result in a decrease in the therapeutic effect of the dopamine agonist.

The use of neuroleptics in combination with other dopamine antagonists (for example, with metoclopramide) can provoke an increase in the intensity of extrapyramidal disorders.

The use of Melperone simultaneously with substances that have cholinolytic activity (for example, atropine) can potentiate the cholinolytic effect. In this case, visual disturbances, increased intraocular pressure, constipation, xerostomia, increased heart rate, salivation, urinary disorder, hypohidrosis, speech difficulties and partial amnesia can develop. The intensity of the effect of Melperone can be weakened by reducing its absorption in the gastrointestinal tract.

Butyrophenones can form compounds with tea, coffee and milk, which reduce their solubility; this makes it difficult for the drug to be absorbed.

Given that melperone only causes a rather weak and short-term increase in prolactin levels, the effect of agents that inhibit prolactin action (for example, gonadorelin) may be reduced. Such an interaction has not developed to date, but it should not be completely ruled out.

Amphetamine stimulants may weaken the antipsychotic effects of the drug.

Epinephrine can cause the development of tachycardia and a paradoxical decrease in blood pressure.

Administration together with melperone may reduce the medicinal effect of phenylephrine.

Combination with dopamine can cause an antagonistic effect with respect to peripheral vasodilation (for example, renal arteries) or, when a large dose of dopamine is administered, vasoconstriction.

It is necessary to exclude the combined use of medications that can prolong the QT interval (including macrolides, antiarrhythmic drugs of type IA or III, as well as antihistamines), lead to the development of hypokalemia (for example, diuretics) or slow down the intrahepatic breakdown of the drug (including fluoxetine with cimetidine).

Storage conditions

Melperone should be stored in a place out of reach of children. Temperature level – no more than 25°С.

Shelf life

Melperone is allowed to be used within a 36-month period from the date of manufacture of the medicinal product. An opened bottle has a shelf life of 2 months.

Analogues

Analogues of the drug are the substances Halopril with Halomond, Senorm and Haloperidol with Droperidol.