Aminazine: instructions for use, indications, price, side effects and reviews

Compound

Contains the active substance chlorpromazine hydrochloride .
The dragee contains 50 or 100 mg of this substance. Auxiliary elements: sunflower oil, talc, gelatin, sucrose, wax, starch syrup, titanium dioxide, iron oxide.

The solution contains 25 mg of chlorpromazine per 1 ml.

Tablets contain 25, 50 or 100 mg of active substance in the form of hydrochloride. Auxiliary elements are: magnesium stearate, cellulose, copovidone, starch, lactose monohydrate, croscarmellose sodium.

Pharmacodynamics and pharmacokinetics

The active component is a phenothiazine derivative. The drug has antiemetic, sedative, antipsychotic, weak hypothermic, vasodilating, local irritant, and moderate anticholinergic effects.

The antipsychotic effect is achieved by blockade of dopamine D2 receptors in the mesocortical and mesolimbic systems. The antipsychotic effect is manifested in the elimination of delusions, hallucinations and other productive symptoms of psychosis.

Aminazine helps relieve various types of psychomotor agitation, reduces the severity of psychotic fear and aggressiveness. The sedative effect is achieved by blocking the adrenergic receptors of the reticular pharmacy, located in the brain stem.

The drug inhibits conditioned reflex activity (especially motor-defensive receptors), reduces the spontaneity of motor activity, reduces sensitivity to exogenous and endogenous stimuli while maintaining consciousness, and relaxes skeletal muscles. Prescribing large dosages causes drowsiness.

Blockade of dopamine D2 receptors in the vomiting center in the trigger zone , as well as blockade of the vagus nerve in the gastrointestinal tract provide an antiemetic effect. Aminazine has a weak effect on m-cholinergic receptors, a pronounced effect is observed on alpha-adrenergic receptors.

The medication is able to completely eliminate the effects caused by epinephrine . The hypothermic effect is provided by blockade of dopamine receptors located in the hypothalamus. The medication increases heart rate, lowers blood pressure, has a pronounced cataleptogenic effect , a weak antihistamine effect, and reduces the permeability of capillary walls. When dopamine receptors are blocked, the production of prolactin by the pituitary gland increases. With intramuscular administration, the sedative effect develops after 15 minutes, with oral administration - after 2 hours. Tolerance to the hypotensive and sedative effects develops after 1 week.

When taken orally, the antipsychotic effect is observed on days 4-7. The most pronounced therapeutic effect lasts from 6 weeks to six months.

The action of aminazine and the effects it causes

Antipsychotic

. Reduces or completely eliminates hallucinations and delusions, especially in endogenous diseases.

Sedative

. Relieves overexcitation (psychomotor agitation), reduces the severity of affect (fear, anger, melancholy), stops aggressiveness.

Antiemetic

. Regardless of the cause of vomiting (poisoning, inflammation of the gastrointestinal tract, psychosomatic reactions, gestosis, etc.), it has an effect that reduces gag reflexes. Also relieves (or reduces) hiccups.

Hypotensive

. Reduces blood pressure, as a result of which tachycardia (increased heart rate) often develops.

Other actions: extrapyramidal (muscle tone changes), hypothermic (body temperature decreases), antipruritic (itching decreases), antiallergic, anticonvulsant, hypnotic, analgesic.

Indications for use of Aminazin

In psychiatric practice, the drug is used in the treatment of psychomotor agitation in patients with schizophrenia . The drug is prescribed for chronic psychosis, hypomanic agitation, acute delusional states, psychopathy, insomnia, anxiety, mental illnesses accompanied by agitation, anxiety, fear, for which tablets are often used.

Also, indications for the use of Aminazin are: alcoholic psychosis , persistent hiccups , “indomitable” vomiting, nausea. For persistent pain, the drug enhances the effect of analgesic medications.

The medicine is prescribed for diseases accompanied by increased muscle tone: tetanus (combination therapy with barbiturates), after suffering cerebrovascular accidents.

Previously, Aminazine was used as part of “lytic” mixtures (for artificial hypothermia ).

In anesthesiology, medication is prescribed to potentiate general anesthesia and for premedication .

In dermatological practice, the drug is used for itchy dermatoses . The drug is prescribed for the treatment of acute “intermittent” porphyria .

Why do we need Aminazine?

Few people today would think to write something about Aminazin, since everyone knows that it does more harm than good. Today, the prescription of this drug by a psychiatrist can only cause surprise and regret; in a way, this is an indicator of the illiteracy of a psychiatrist. However, since Aminazine was essentially the first antipsychotic, in my opinion, it is still worth talking about.

Mechanism of action and side effects

Aminazine (Chlorpromazine) belongs to the category of typical antipsychotics or antipsychotics, also known as first-generation antipsychotics (FGA). It exerts its antipsychotic effect through postsynaptic blockade of D2 receptors in the mesolimbic pathway. However, blockade of D2 receptors in the nigrostriatal pathway is responsible for neurological, extrapyramidal side effects. The antiemetic effect of Chlorpromazine is due to the combined blockade of histamine H1, dopamine D2 and muscarinic M1 receptors in the “center of vomiting”. Aminazine is highly soluble in fats and accumulates in fats, so it is excreted from the body very slowly .

Aminazine in the blood

The liver enzyme P450 CYP2D6 metabolizes Aminazine and has a half-life of approximately 30 hours. Aminazine is excreted from the body in urine and bile. The researchers noted that patients receiving chronic treatment with chlorpromazine had lower plasma levels compared to patients receiving a single dose of oral chlorpromazine. Also, simultaneous use of anticholinergics may affect the concentration of chlorpromazine in plasma. However, plasma levels and response thresholds for clinical improvement in symptoms and toxicity with Chlorpromazine vary in both children and adults.

Weak and harmful

Chlorpromazine is a low-potency antipsychotic that primarily causes non-neurological side effects (“vegetables”). However, Aminazine primarily causes dry mouth, dizziness, urinary retention, blurred vision and constipation by blocking muscarinic receptors. In older people there is a risk of angle-closure glaucoma. It also causes sedation due to blockade of histamine H1 receptors.

The effect of Aminazine on the nervous system

Although Aminazine is a drug with low activity, it can still cause extrapyramidal side effects (EPS) such as acute dystonia, akathisia, parkinsonism and tardive dyskinesia (TD). Neurological side effects may take hours to days to develop. Acute dystonia refers to muscle stiffness or spasm in the muscles of the head, neck, and eyes, which may begin within a few hours of starting the medication. Akathisia includes motor restlessness (restlessness), severe anxiety and fussiness. Parkinsonism includes bradykinesia, cogwheel rigidity, and a shuffling gait. Tardive dyskinesia occurs as a result of long-term use of antipsychotic drugs and involves involuntary, repetitive, abnormal movements of the face and limbs. Patients taking Aminazine are also at risk of developing neuroleptic malignant syndrome, a life-threatening condition in which the patient experiences lead-pipe muscle stiffness.

The effect of Aminazine on blood vessels and the heart

When administered intramuscularly or intravenously, Aminazine can sharply reduce blood pressure (cause hypotension) and headache. Aminazine should not be prescribed to patients taking antihypertensive drugs due to the risk of a sharp decrease in blood pressure. Aminazine can increase the QT interval on the electrocardiogram, and, consequently, impair the conduction of the heart muscle. It is better not to use Chlorpromazine in patients with cerebrovascular and cardiovascular diseases. It is also worth adding that Aminazine can damage the bone marrow and cause agranulocytosis, which makes a person especially susceptible to various infections.

Allergy from taking Aminazine

Patients allergic to phenothiazines may develop hypersensitive anaphylactic reactions to chlorpromazine. Such patients can only be treated by stopping the drug and prescribing steroids or antihistamines.

Liver hit

Drug-induced hepatotoxicity occurs as a result of inflammation and damage to the liver, which can significantly increase alanine aminotransferase (ALT) levels. This can be prevented by regular monitoring with liver function tests, and if liver damage is detected early, the drug should be discontinued and symptomatic treatment initiated. Studies have shown that Chlorpromazine can also cause cholestatic jaundice due to obstruction of bile flow.

Hormonal consequences of taking Aminazine

Antagonism of D2 receptors in the tuberoinfundibular pathway is thought to be responsible for the increase in prolactin levels. This hyperprolactinemia can cause several endocrine side effects such as decreased libido. In men, elevated prolactin levels can cause gynecomastia, galactorrhea and erectile dysfunction. In rare cases, it can cause priapism. In women, an increase in prolactin levels can lead to irregular menstruation, oligomenorrhea, amenorrhea and galactorrhea, as well as fibrocystic mastopathy, osteoporosis.

Everything is in a fog

Long-term use of Chlorpromazine may cause deposits on the cornea and clouding of the lens.

Doesn't match

Aminazine should not be administered concomitantly with drugs that depress the central nervous system or in patients with poorly controlled seizures. This drug should not be used to treat psychosis associated with dementia. The D2 receptor blocking effect of Chlorpromazine may interfere with the therapeutic efficacy of dopamine agonist drugs such as levodopa or cabergoline. Antidepressants, in particular selective serotonin reuptake inhibitors such as Citalopram and Escitalopram, are contraindicated for use with Aminazine.

How can I help a person taking Aminazine?

In case of overdose of Aminazine, provide adequate ventilation. There is no specific antidote for Aminazine poisoning, and treatment is mainly symptomatic with regular monitoring of the heart and breathing. Treatment of tardive dyskinesia is achieved by stopping Chlorpromazine and starting a second generation antipsychotic along with Valbenazine or Deyetrabenazine.

Contraindications

Aminazine is not used in comatose states of any etiology, with severe depression of the functions of the nervous system, with severe pathology of the cardiovascular system, with intolerance to the active substance, with progressive diseases of the spinal cord and brain of a systemic nature, with breastfeeding, with ulcerative lesions of the digestive tract .

Due to the risk of developing hepatotoxic reactions, Aminazine is prescribed with caution for alcoholism. For breast cancer, pathological changes in the blood, prostatic hyperplasia , angle-closure glaucoma, Parkinson's disease, myxedema, epilepsy, vomiting, cachexia, Reye's syndrome, and elderly patients, the drug is prescribed with caution.

Aminazine-valenta film-coated tablets 100 mg N10

Contraindicated combinations The simultaneous use of chlorpromazine with citalopram and escitalopram is contraindicated. Not recommended combinations Long-term combination with analgesics and antipyretics is undesirable - the development of hyperthermia is possible. Phenothiazine derivatives are antagonists of the action of epinephrine and other sympathomimetics and antiepileptic drugs (lowering the seizure threshold). When treating with Aminazin®, the administration of epinephrine should be avoided, as the effect of epinephrine may be distorted, which can lead to a drop in blood pressure. The use of epinephrine in case of overdose is not allowed. Concomitant use of chlorpromazine with drugs that prolong the QT interval may increase the risk of developing ventricular arrhythmias, including torsade de pointes (TdP). Concomitant use of chlorpromazine with antiarrhythmic drugs of class IA (quinidine, disopyramide, prokinamide) and class III (for example, amiodarone, sotalol, dofetilide), certain antimicrobial drugs (sparfloxacin, moxifloxacin, erythromycin), tricyclic antidepressants (such as amitriptyline), tetracyclic antidepressants (such as maprotiline), other antipsychotics (such as phenothiazines, pimozide, sertindole), antihistamines (such as terfenadine), cisapride, bretylium tosylate, antimalarials (such as quinine and mefloquine). The simultaneous use of chlorpromazine with bromocriptine increases the plasma concentration of prolactin and interferes with the action of bromocriptine. Chlorpromazine reduces the antiparkinsonian effect of levodopa (due to the blockade of dopamine receptors caused). With simultaneous use of the drug Aminazin® with other drugs that have a depressant effect on the central nervous system (general anesthesia, narcotic analgesics, ethanol (alcohol) and drugs containing it, barbiturates, tranquilizers, etc.), increased depression of the central nervous system, as well as respiratory depression, may occur. . Chlorpromazine causes increased renal excretion of lithium; in addition, combination with lithium preparations increases the risk of extrapyramidal complications. Combinations requiring precautions The simultaneous use of chlorpromazine with antiarrhythmic drugs of classes Ia and III, beta-blockers, some calcium channel blockers, digitalis drugs, pilocarpine, anticholinesterase drugs may be accompanied by bradycardia and an increased risk of developing ventricular arrhythmia, including torsades de pointes. When combining these drugs with chlorpromazine, ECG monitoring is recommended. When used together with hypoglycemic drugs, chlorpromazine in high doses (100 mg/day) weakens the hypoglycemic effect by reducing insulin secretion and increasing blood glucose levels (see section Special instructions). Antacids, antiparkinsonian drugs and lithium salts may reduce the absorption of chlorpromazine. Antacids should not be used two hours before and after taking Aminazin®. Combinations to consider Barbiturates may decrease serum concentrations of chlorpromazine. Prescribing chlorpromazine in combination with tricyclic antidepressants, maprotiline or monoamine oxidase inhibitors (MAOIs) increases the risk of developing neuroleptic malignant syndrome. When using chlorpromazine in combination with drugs for the treatment of hyperthyroidism, the risk of developing agranulocytosis increases. When using chlorpromazine in combination with drugs that cause extrapyramidal reactions, an increase in the frequency and severity of extrapyramidal disorders is possible. Phenothiazine derivatives increase the hypotensive effect of anesthetics, slow calcium channel blockers and other antihypertensive drugs and trazodone. Chlorpromazine reduces the hypotensive effect of neuronal adrenergic blockers, such as guanethidine, the effects of amphetamines, clonidine. With the simultaneous use of chlorpromazine and angiotensin-converting enzyme (ACE) inhibitors, severe orthostatic hypotension occurs. The simultaneous use of beta-blockers and chlorpromazine increases the risk of arterial hypotension, including orthostatic, due to the additive vasodilatory effect of chlorpromazine and the decrease in cardiac output caused by beta-blockers. The simultaneous use of beta-blockers and chlorpromazine increases the risk of developing irreversible retinopathy and tardive dyskinesia. The simultaneous use of chlorpromazine with nitrates increases the risk of orthostatic hypotension due to increased vasodilator effect. Concomitant use of chlorpromazine with thiazide diuretics increases hyponatremia. Concomitant use with antimuscarinic drugs may aggravate the development of anticholinergic side effects (urinary retention, provocation of an acute attack of glaucoma, dry mouth, constipation, etc.). Various drugs have anticholinergic properties: atropine, tricyclic antidepressants, H1-histamine blockers, antimuscarinics, antiparkinsonian anticholinergic antispasmodics, disopyramide, phenothiazine neuroleptics and clozapine. When using clopromazine in combination with ephedrine, the vasoconstrictor effect of ephedrine may be weakened. Chlorpromazine has moderate anticholinergic activity, which may be increased by other anticholinergic drugs. Aminazine® also enhances the anticholinergic effects of other drugs, while its own antipsychotic effect may decrease. Chlorpromazine may mask some manifestations of ototoxicity (tinnitus, dizziness) of drugs that have ototoxic effects (for example, antibiotics with ototoxic effects). Other hepatotoxic drugs increase the risk of developing hepatotoxicity. Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression. With the simultaneous use of chlorpromazine with antimalarial drugs, the concentration of chlorpromazine in the blood plasma increases with the risk of developing toxic effects. With simultaneous use of chlorpromazine with cimetidine, a change (increase or decrease) in the concentration of chlorpromazine in the blood plasma is possible. With the simultaneous use of chlorpromazine with prochlorperazine, a related chemical structure, transient metabolic encephalopathy, characterized by loss of consciousness within 48 to 72 hours, may occur. Special instructions During treatment, it is necessary to regularly monitor blood pressure, pulse, liver and kidney function. It is also necessary to monitor the blood picture (at the beginning weekly, and then every 3-4 months) if during therapy the number of leukocytes decreases to 3.0 -3.5x109 / l, and the number of neutrophils decreases to 1.5 -2.0x109 /l, monitoring of these indicators should be carried out 2 times a week; in case of leukocytosis and granulocytopenia, treatment should be interrupted. Each patient should be informed that if they have a fever, sore throat or other manifestations of infectious diseases, they should immediately notify their doctor. In the event of hyperthermia, which may be one of the symptoms of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, changes in consciousness, muscle rigidity), the drug Aminazine should be discontinued immediately. Early manifestations preceding the onset of hyperthermia may include side effects such as increased sweating and instability of blood pressure (BP). Although the etiology of the dependence of such side effects on antipsychotics is most often unknown, there are a number of risk factors: individual predisposition, dehydration, organic brain damage. Neuroleptic malignant syndrome can occur at any time during treatment with antipsychotic drugs and can be fatal. If signs and symptoms of tardive dyskinesia occur, consider reducing the dose or discontinuing all antipsychotic medications. Tardive dyskinesia sometimes occurs after discontinuation of the antipsychotic and disappears with repeated use or increased dosage. Prescribing antiparkinsonian and anticholinergic drugs for the development of tardive dyskinesia is contraindicated (the condition may worsen). Antiparkinsonian drugs - trihexyphenidyl and others - are used as correctors for extrapyramidal disorders, the occurrence of which is possible with the use of the drug Aminazin®. Aminazine®, depending on the dose, may increase the prolongation of the QT interval, which increases the risk of ventricular arrhythmias, including torsades de pointes. Bradycardia, hypokalemia, and congenital or acquired long QT period also increase. Therefore, before starting treatment, it is necessary to ensure the absence of: - bradycardia below 55 beats per minute - hypokalemia - congenital prolongation of the QT interval. Except in emergency situations, it is recommended to perform an ECG during the preliminary examination of patients requiring treatment with an antipsychotic. In randomized clinical trials in elderly patients with dementia, atypical antipsychotic drugs (AEDs) were found to have an increased risk of stroke compared with placebo. The mechanism for this increased risk is not known. An increased risk with other antipsychotics or in other age groups cannot be excluded. Aminazine should be used with caution in patients with risk factors for stroke, in elderly patients with dementia, since the risk of mortality increases in elderly patients with psychoses associated with dementia and receiving antipsychotic drugs. Placebo-controlled studies, which were conducted primarily in patients taking atypical antipsychotic drugs, showed a 1.6- to 1.7-fold increased risk of mortality compared with placebo. At the end of treatment, lasting an average of 10 weeks, the risk of mortality was 4.5% in the chlorpromazine group, compared with 2.6% in the placebo group. Although the causes of death in clinical studies with atypical antipsychotics varied, the majority of these deaths were the result of cardiovascular problems (eg, heart failure, sudden death) or infections (eg, pneumonia). There is a risk of venous thromboembolism (VTE) during treatment with antipsychotics. In patients receiving antipsychotic drugs, especially those with acquired risk factors for VTE, preventive measures should be taken and any potential risk factor for VTE should be assessed before and during treatment with Aminazine®. Except in exceptional circumstances, Aminazine® should not be used in Parkinson's disease. The occurrence of intestinal obstruction, which can be detected by bloating and abdominal pain, requires emergency care. Predisposing factors for the development of arrhythmia when taking Aminazin® are: hypokalemia (including when using diuretics that cause hypokalemia), bradycardia (including those caused by drugs), an existing (congenital or acquired) increase in the duration of the QT interval. The simultaneous administration of chlorpromazine with dopaminergic non-antiparkinsonian drugs (cabergoline, quinagolide) is not recommended due to the mutual antagonism of dopamine agonists and antipsychotics. Concomitant use with other antipsychotics that can cause torsades de pointes (amisulpride, cyamemazine, droperidol, fluphenazine, propericiazine, haloperidol, levomepromazine, pimozide, pipamperone, pipothiazine, sertindole, sulpiride, sultopride, tiapride) is not recommended. Concomitant use with antiparasitic drugs (halofantrine, lumefantrine, pentamidine) is not recommended. Also, simultaneous use with antifungal agents from the azole group is not recommended (increased risk of arrhythmia). If it is impossible to avoid the co-administration of the above combinations, it is recommended to carry out regular ECG monitoring with monitoring of the duration of the QT interval. When using non-potassium-sparing diuretics, correction of hypokalemia and ECG monitoring are necessary before starting chlorpromazine therapy. Monitoring during treatment with Aminazin® should be increased: - in patients with epilepsy and a history of seizures, due to the possibility of a decrease in the seizure threshold. The occurrence of seizures requires cessation of treatment. - in elderly patients with: a) high susceptibility and the effect of orthostatic hypotension (increased risk of excessive sedation and hypotensive effects), b) chronic constipation (risk of paralytic intestinal obstruction), c) possible prostatic hypertrophy - in patients with cardiovascular diseases diseases taking quinidine, due to a possible increase in the hypotensive effect - in the case of liver failure and/or severe renal failure, due to the risk of accumulation. For long-term treatment, regular ophthalmological monitoring is recommended. It should be taken into account that the use of phenothiazine derivatives can lead to hyperglycemia or impaired glucose tolerance, development or exacerbation of diabetes mellitus, hypercholesterolemia, fecal impaction, severe intestinal obstruction and megacolon. Since in high doses (100 mg/day) chlorpromazine can cause an increase in blood glucose levels by reducing insulin secretion, in patients with diabetes mellitus it is necessary to adjust insulin doses before and after completion of therapy. If necessary, the dose of the antipsychotic should also be adjusted in patients taking sulfonylureas. Chlorpromazine should not be used as monotherapy if depression predominates. Aminazine® should be used with caution in case of hypersensitivity to other phenothiazine drugs or severe respiratory diseases. Due to the risk of photosensitivity, ultraviolet irradiation should be avoided. Aminazine® can worsen the course or promote the manifestation of latent myasthenia gravis, as well as cause myasthenic syndrome. To avoid the development of withdrawal syndrome, it is necessary to stop treatment with Aminazin® gradually. The mutual antagonism of levodopa and antipsychotics must be taken into account. Dopamine may cause or worsen psychotic disorders. To treat patients suffering from parkinsonism, it is necessary to use minimal effective doses of both drugs. If it is necessary to treat patients with parkinsonism who have received dopamine with antipsychotics, the dose of the latter should be gradually reduced to a minimum (abrupt withdrawal of dopamine may increase the risk of developing neuroleptic malignant syndrome). In patients with pheochromacetoma taking Aminazine®, false positive results of catecholamine levels in the blood may be observed. During therapy, it is necessary to stop drinking alcohol, since chlorpromazine enhances the inhibitory effect of alcohol on the central nervous system. Impact on the ability to drive vehicles and operate machinery: During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Side effects of Aminazine

Let's look at the side effects of Aminazine. At the first stages of therapy, dry mouth, increased drowsiness , accommodation paresis, constipation, dizziness, appetite disturbances, tachycardia, a severe form of orthostatic hypotension, decreased potency, urinary retention, sleep disorders, allergic reactions , frigidity , drop in blood pressure are noted.

Long-term therapy with chlorpromazine causes neuroleptic depression , cramps of the tongue, neck muscles, floor of the mouth, extrapyramidal disorders , akathisia, akineto-rigid phenomena, delayed reaction to stimuli, mental changes, amenorrhea , hypercoagulation, inhibition of bone marrow hematopoiesis, cardiac arrhythmias, cholestatic jaundice, gynecomastia, hyperplolactinemia , galactorrhea, skin pigmentation, oliguria, diarrhea, vomiting, neuroleptic malignant syndrome. When administered intramuscularly, infiltrates may form; with intravenous infusion - phlebitis .

Aminazine

Instructions for use of Aminazin (Method and dosage)

The drug is taken orally, administered intramuscularly, intravenously.

Aminazine tablets, instructions for use

The initial daily dosage in psychiatric practice is 25-100 mg (for 1-4 doses). Gradually, the amount of the drug is increased every 3-4 days by 25-50 mg until the desired effect is achieved. In case of anxiety before surgical interventions, the medication is prescribed 2-3 hours before surgery. The maximum one-time intake is 300 mg, per day - 1.5 g.

Solution

A 2.5% solution is administered intravenously and intramuscularly.

The initial dose is 25-50 mg. Before intramuscular administration, the drug solution is diluted in 2-5 ml of procaine (0.25-0.5%), or in a 0.9% sodium chloride solution. Aminazine is administered deeply intramuscularly. Before surgical interventions in cases of anxiety, patients are administered the drug intramuscularly at the rate of 0.55 mg per 1 kg of weight 2 hours before the intended surgical treatment. For tetanus, 0.55 mg/kg is administered intramuscularly every 8 hours, the infusion rate is 1 mg/2 minutes.

Maximum one-time intramuscular injection is 150 mg, per day - 1 g.

The maximum one-time intravenous dose is 100 mg, per day - 250 mg.

In pediatric practice, only special, pediatric forms of the drug are used.

Neuromolecules: aminazine

The revolution that occurred in most branches of medicine in the early 40s of the last century with the discovery of antibiotics did not affect psychiatry in any way. By the end of this fateful decade for doctors, the methods of psychiatrists would still give odds to the arsenal of the most brutal exorcist of the heyday of the Inquisition. Lobotomy, electroshock and insulin comatose therapies were used everywhere. These barbaric methods of treatment were supplemented by a modest range of psychoactive substances of the most general and far from harmless action, such as morphine, cocaine or codeine. However, within a few years, a real psychopharmacological revolution took place in this seemingly hopeless branch of medicine. These dramatic changes are directly related to the invention of our today’s hero of the Neuronovosti.ru portal project together with the Institute of Bioorganic Chemistry of the Russian Academy of Sciences on neuromolecules - chlorpromazine.

Aminazine molecule

The lineage of chlorpromazine, like many other drugs of this era, goes back to dyes. At the turn of the 19th and 20th centuries, experiments by Nobel laureate Paul Ehrlich on staining microorganisms revealed the specific affinity and toxicity of some dyes for certain microorganisms. Ehrlich inspired scientists around the world to search for a “magic bullet” - a substance that, while remaining safe for the human body, would be selectively toxic to pathogenic microorganisms. One of the first such drugs was methylene blue, a popular fabric dye.

Paul Ehrlich

Methylene blue

Its solution turned out to be a good antiseptic and an effective antimalarial drug. A few years later, its chemical precursor, phenothiazine, was synthesized. The antimalarial activity of phenothiazines was no good, but they were good at poisoning insects, and at the same time intestinal parasites. But most importantly, it gave rise to a whole bunch of derivative drugs. A separate article can be written about each of them, but today we are only interested in chlorpromazine synthesized on its basis.

Chlorpromazine (aminazine)

It was created in December 1950 as a means intended for a narrow task - combating postoperative shock. But the new substance turned out to be much more interesting than its creators had hoped. In combination with surgical anesthesia, the drug significantly prolonged its effect and also led to a decrease in the patient’s body temperature to 28–30°C. This “artificial hibernation” sharply slows down the metabolism, which makes complex heart operations that require cardiac arrest easier and safer. At the same time, the substance had a sedative, anticonvulsant and antiemetic effect. To reflect the breadth of action of the drug, it was launched on the market in 1952 under the brand name Largactil (from the English large - wide).

A drug with such a set of properties could be useful in psychiatry. The first tests that psychiatrist Frank Hades did gave a brilliant result: after a three-week course of the drug, a 24-year-old “violently insane” diagnosed with schizophrenia, previously treated with opioids, barbiturates and electric shock, returned to normal life and was discharged home. Hades managed to obtain approval from the FDA to use the drug to treat schizophrenia. Within a few years, the drug became widely used and even went on sale. In 1955 alone, the American company SKF sold chlorpromazine (under the brand name “Thorazine” - that’s the name) for $75 million. By 1964, 50 million people worldwide were taking this “psychiatric aspirin.” Chlorpromazine became the founder of a whole family of antipsychotic drugs called neuroleptics.

Advertising for Thorazine in the USA

To understand the mechanism of action of chlorpromazine, better known in Russia as “aminazine,” we need to remember how the cells of our nervous system “communicate” with each other. The neurons that form the active part of our nervous system have processes (dendrites), the outgrowths on which (dendritic spines) come together. In the area of convergence between the processes of the dendrite and the axon (or body of neurons), which is called the synapse, one nerve cell can transmit signals to another. They are transmitted through special substances - mediators. One cell releases the transmitter, enclosed in special vesicles, directly onto the surface of another. But in order to receive this molecular signal, the cell must have special proteins on its surface that recognize a certain type of mediator. They are called receptors.

Synapse diagram

The body has a whole set of mediators that force the recipient cell to generate a nerve impulse; they are called excitatory. There are also mediators that force the recipient to block the conduction of an impulse; they are called inhibitory. At the same time, each neurotransmitter corresponds to a family (or even several) of receptors that recognize it. Most mental disorders are in one way or another associated with disturbances in the exchange of neurotransmitters in the brain, or with changes in the structure and function of receptors. Many poisons, drugs and medicines resemble mediators in their structure. They interact with a certain type of receptor and block them, making them insensitive to the natural mediator, or, on the contrary, activate longer and stronger than any existing mediator. As a result, the functioning of the nervous system changes in a certain way.

To date, scientists have found that the surprisingly versatile effect of chlorpromazine is explained by its action on several receptor systems in the body. In 1963, Swedish researchers Karlsson and Lindquist found that chlorpromazine, together with another popular antipsychotic, haloperidol, binds to the dopamine receptor. This and further work on the dopamine receptor will bring Arvid Carlsson the Nobel Prize in 2000 (an article about this scientist will appear on our website). Indeed, among other things, dopamine receptors are responsible for the regulation of attention and general physical activity, as well as the formation of emotions. By blocking these receptors (mainly type D2 dopamine receptors), chlorpromazine compensates for the changes that occur during psychosis, suppressing attacks of panic and aggression.

Arvid Karlsson

At the same time, chlorpromazine blocks serotonin receptors (5-HT1 and 5-HT2 types), H1 type histamine receptors, α1 and α2 adrenergic receptors and M1 and M2 muscarinic acetylcholine receptors. Oddly enough, for a pharmacist this all sounds just as scary as for a person not familiar with neurochemistry. After all, logic says that the wider the drug’s spectrum of action, the more side effects. In the dreams of pharmacologists, a drug should generally have one type of target receptor on which it acts. However, in practice it turned out that the side effects of chlorpromazine are not so bad compared to its benefits.

The advent of chlorpromazine revolutionized psychiatry. This drug proved that many mental illnesses are amenable to pharmacological treatment, thereby returning thousands of hopeless patients to psychiatric clinics home. If in 1955 there were 500,000 psychiatric patients in US clinics (and we remember how many lobotomies were performed), then by 1975 their number had decreased to 200,000! Despite the synthesis of many derivatives of this substance, it is actively used to this day. And to assess the antipsychotic activity of drugs, pharmacologists use the chlorpromazine scale, comparing the effect of the drug with a reference dose of 100 mg of chlorpromazine.

Text: Dmitry Lebedev, graduate student of the Laboratory of Ligand-Receptor Interactions, IBCh RAS.

Literature:

López-Muñoz, Francisco, et al. "History of the discovery and clinical introduction of chlorpromazine." Annals of Clinical Psychiatry 17.3 (2005): 113-135.

Yorston, Graeme, and Alison Pinney. "Chlorpromazine equivalents and percentage of British National Formulary maximum recommended dose in patients receiving high-dose antipsychotics." The Psychiatrist 24.4 (2000): 130-132.

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Overdose

An overdose is manifested by blurred visual perception, hyperreflexia or areflexia . Cardiotoxic effects in the form of shock, drop in blood pressure, development of heart failure , arrhythmia, cardiac arrest, ventricular fibrillation, and changes in the QRS complex on the electrocardiogram are also noted

Neurotoxic effects include coma, stupor, drowsiness, disorientation , convulsions, confusion, agitation, respiratory depression, pulmonary edema, vomiting, muscle rigidity, hypothermia, or hyperpyrexia .

The administration of enterosorbents and gastric lavage are required. When arrhythmia develops, phenytoin is administered intravenously; when heart failure develops, the use of cardiac glycosides . When blood pressure drops, vasopressors ( phenylephrine , norepinephrine) are given intravenously. Diazepam is indicated for the development of seizures. Diphenhydramine and diphenyltropine are effective for parkinsonism For five days, control over the functioning of the cardiovascular system and respiratory system is required, and consultation with a psychotherapist is required. Dialysis has not proven effective.

Interaction

Aminazine may weaken the vasoconstrictor effect of the drug Ephedrine . Some manifestations of ototoxicity (severe dizziness, tinnitus) when taking ototoxic medications may be masked during treatment with chlorpromazine.

The drug reduces the severity of the antiparkinsonian effect of levodopa (as a result of blockade of dopamine receptors). A similar effect is observed when taking clonidine , amphetamine, and guanethidine.

The medication enhances the anticholinergic effect of other drugs, but at the same time there is a decrease in its own antipsychotic effect. The medication is compatible with antidepressants , antipsychotics, and anxiolytics. Long-term use of antipyretics and analgesics is not recommended due to the risk of hyperthermia .

The risk of developing neuroleptic malignant syndrome increases significantly when combined with tricyclic antidepressants, MAO inhibitors, and manprotiline.

Lithium preparations, antiparkinsonian drugs, antacid medications interfere with the absorption of chlorpromazine.

Aminazine-Valenta tablets 50 mg 10 pcs ➤ instructions for use

special instructions

Therapy with the drug requires control over the pulse, blood pressure, and the functioning of the hepatic and renal systems. To prevent a sharp drop in blood pressure after intravenous and intramuscular injections, the patient is placed on the couch for 1.5-2 hours.

Due to the fact that the drug can cause photosensitivity , it is recommended to avoid ultraviolet rays and radiation. Ethanol intake is not allowed during therapy. It is necessary to completely eliminate the possibility of chlorpromazine getting on mucous membranes and skin.

The drug affects driving.

Described on Wikipedia as Chlorpromazine.

INN: Chlorpromazine.

Recipe in Latin:

Rp.: Sol. Aminazini 2.5% 1.0 D. td N 10 in amp. S.

Etaperazin

Elderly patients with dementia-related psychosis treated with antipsychotic drugs have an increased risk of death.

Extrapyramidal disorders occur more often when taking high doses. Tardive dyskinesia occurs more often in older patients, especially women, while dystonia occurs more often in younger people. If signs or symptoms of tardive dyskinesia occur, consider discontinuing antipsychotic treatment (however, some patients may require continued treatment despite the presence of the syndrome).

Perphenazine may lower the seizure threshold, so caution should be exercised when using the drug in patients with a predisposition to seizure disorders and during alcohol withdrawal. With simultaneous treatment with perphenazine and anticonvulsants, an increase in the dose of the latter may be required.

During therapy with perphenazine, alcohol intake should be avoided, because Additive effects and hypotension may occur. The risk of suicide and the risk of antipsychotic overdose may be increased in patients who abuse alcohol during treatment due to the potentiation of the depressive effect of the drug on the central nervous system.

Caution should be exercised when prescribing the drug to patients with depression. The possibility of suicide in such patients remains during treatment, so it is necessary to exclude them from access to a large number of medications during treatment until complete remission occurs.

Perphenazine should be used with caution in patients with a history of serious side effects from other phenothiazines. Some of the adverse reactions of perphenazine occur more often when taking high doses. Perphenazine should be used with great caution in persons exposed to heat or cold because Phenothiazine derivatives inhibit the temperature regulation mechanism and, depending on the ambient temperature, can lead to hyperthermia and heat stroke or hypothermia and respiratory failure. A significant increase in body temperature can be caused by individual hypersensitivity. If hyperthermia occurs, treatment should be discontinued immediately. Perphenazine increases the body's sensitivity to sunlight. It is recommended to use sunscreen, especially if patients have fair skin, and wear protective clothing when outdoors, as well as avoid prolonged exposure to the sun, tanning beds, and the use of ultraviolet lamps.

Perphenazine should be used with caution in patients suffering from respiratory disorders due to the possible development of acute pulmonary infection, as well as in chronic respiratory diseases such as bronchial asthma or emphysema.

Antipsychotic drugs increase the concentration of prolactin in the blood, which persists with long-term use. Symptoms may include breast enlargement, dysmenorrhea, decreased libido, or nipple discharge.

Caution should be exercised when prescribing the drug to patients receiving atropine or similar drugs, as well as those who have contact with phosphorus-containing insecticides (an additive anticholinergic effect is possible).

During treatment, liver and kidney functions (with long-term therapy), peripheral blood patterns, and prothrombin index should be monitored. If signs or symptoms of blood dyscrasia occur, treatment should be discontinued and appropriate therapy instituted. Treatment should also be stopped if there are abnormalities in liver tests or if the blood urea nitrogen level is abnormal. Most cases of agranulocytosis were observed between 4 and 10 weeks of therapy. During this period, patients should be especially careful to monitor for sore throat or symptoms of infection. If the number of leukocytes decreases significantly, the drug should be discontinued and appropriate therapy should be started.

Jaundice that develops (rarely) during treatment (between 2 and 4 weeks of therapy) is usually considered a hypersensitivity reaction. In this case, the clinical picture is similar to that of infectious hepatitis, but the results of liver function tests are characteristic of obstructive jaundice. It is usually reversible, but cases of chronic jaundice have been reported.

Reviews about Aminazine

The drug has a very powerful effect, helping to eliminate signs of psychomotor agitation. However, reviews of Aminazine are very different.

Some people maintain that the drug is very effective for schizophrenia, Alzheimer's disease, epilepsy, psychosis, and relieves stress and anxiety. Others consider the drug sometimes even simply terrible; they say that it provokes epileptic seizures, hand tremors, a state of increased drowsiness, and various personality disorders.

In any case, this medication should only be used under the supervision of a physician.

Aminazine price, where to buy

A package of 10 ampoules of 2 ml 25 mg/ml costs approximately 60 rubles.

10 tablets of 25 mg cost about 150 rubles.

The price of Aminazin in tablets is approximately 70 rubles per package of 10 pieces of 100 mg.

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine
Online pharmacies in KazakhstanKazakhstan

ZdravCity

Aminazine tablets p.p.o.
50 mg 10 pcs. PJSC Valenta Pharm/JSC Valenta Pharmaceuticals/JSC Valenta Pharm 239 rub. order

Pharmacy Dialogue

Aminazine (tab.p.pl/vol. 50 mg No. 10) Valenta Pharmaceuticals OJSC
RUB 224 order
Aminazine (amp. 2.5% 2ml No. 10)Novosibkhimpharm OJSC
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Aminazine (tab.p.pl/vol. 25 mg No. 10) Valenta Pharmaceuticals OJSC
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Pharmacy24

Aminazine 2.5% 2 ml N10 injection solution PAT "Galichfarm", Ukraine
34 UAH. order

PaniPharmacy

Aminazine ampoule Aminazine solution d/in. 2.5% amp. 2ml No. 10 Ukraine, Galichfarm JSC
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Aminazine tablet. p/o 0.1g No. 10 in pack.
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Aminazine ampoule Aminazine solution d/in. 2.5% amp. 2ml No. 10 Ukraine, Health of the people LLC
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