Neuroleptic - what is it? What is the mechanism of action of neuroleptics?

Psychotropic drug, whose purpose - the treatment of psychotic disorders, is called antipsychotic (also antipsychotic or neuroleptic). What is it and how does it work? Let's figure it out.

Neuroleptic. What it is? History and characteristics

Neuroleptics in medicine appeared relatively recently. Before their discovery, for the treatment of psychoses, the most commonly used drugs were plant origin (for example, bleach, belladonna, opiates), intravenous calcium, bromides, and narcotic sleep.

In the early 50-ies of the 20th century, antihistamines or lithium salts were used for these purposes.

One of the earliest antipsychotics was chlorpromazine (or aminazine), which had previously been considered a common antihistamine. Widely applied it began in 1953, mainly as a sedative or as a neuroleptic (in schizophrenia).

The next neuroleptic was the alkaloid reserpine, but soon gave way to other, more effective drugs, as it practically did not work.

In the beginning of 1958, other antipsychotics of the first generation appeared: trifluoperazine (triftazine), haloperidol, thiopperazine, and others.

The term "neuroleptic" was proposed in 1967 (when the classification of psychotropic drugs of the first generation was created) and he treated drugs not only with antipsychotic action, but also capable of causing neurological disorders (acacia, neuroleptic Parkinsonism, various dystonic reactions, and others). Usually these disorders caused substances such as aminazine, haloperidol and trifazin. Moreover, treatment with them is almost always accompanied by unpleasant side effects: depression, anxiety, pronounced fear, emotional indifference.

Earlier neuroleptics could also be called "big tranquilizers", so neuroleptics and tranquilizers are the same. Why? Because they also cause pronounced sedative, hypnotic and tranquilizing-anti-anxiety effects, as well as a very specific state of indifference (ataraxia). Now this name is not applied to neuroleptics.

All antipsychotics can be divided into typical and atypical. Typical antipsychotics we have partially described, now consider an atypical antipsychotic. What it is? This is a group of more "soft" drugs. They do not act as much on the body as they do. They belong to the neuroleptics of the new generation. The advantage of atypical antipsychotics is that they have less effect on dopamine receptors.

Neuroleptics: evidence

All neuroleptics have one basic property - an effective effect on productive symptoms (hallucinations, delusions, pseudo-hallucinations, illusions, behavioral disorders, mania, aggressiveness and agitation). In addition, neuroleptics (mostly atypical) may be prescribed for the treatment of depressive or deficit symptoms (autism, emotional flattening, desocialisation, etc.). However, their effectiveness in relation to the treatment of deficit symptoms is a big question. Experts suggest that antipsychotics can eliminate only secondary symptoms.

Atypical antipsychotics, whose mechanism of action is weaker than the typical ones, is also used to treat bipolar disorder.

The American Psychiatric Association prohibits the use of neuroleptics to treat the psychological and behavioral symptoms of dementia. Also, they should not be used for insomnia.

It is unacceptable to be treated with two or more antipsychotic drugs at the same time. And remember that antipsychotics are used to treat serious diseases, it's just not recommended to take them.

Main effects and mechanisms of action

Modern neuroleptics have one common mechanism of antipsychotic action, because they can reduce the transmission of nerve impulses only in those brain systems in which impulses transmit dopamine. Let's take a closer look at these systems and the effect of neuroleptics on them.

• Mesolimbic path. Reduction of the transmission of nerve impulses in this way occurs with the administration of any antipsychotic drug, since it means the removal of productive symptoms (for example, hallucinations, delusions, etc.)
• The mesocortical path. Here, a reduction in the transmission of impulses leads to the manifestation of symptoms of schizophrenia (negative disorders such as apathy, desocialisation, speech impairment, affect alleviation, anhedonia) and cognitive impairments (attention deficit, memory function abnormalities, etc.) appear. The use of typical antipsychotics, especially prolonged, leads to an increase in negative disorders, as well as serious impairment of brain functions. The abolition of neuroleptics in this case will not help.
• Nigrostriar path. The blockade of dopamine receptors in this case usually leads to the appearance of side effects typical for neuroleptics (akathisia, parkinsonism, dystonia, salivation, dyskinesia, trichus of jaws , etc.). These side effects are observed in 60% of cases.
• Tuberoinfundibular path (transfer of impulses between the limbic system and the pituitary). Blocking the receptors leads to an increase in the hormone prolactin. Against this background, a huge number of other side effects, such as gynecomastia, galactorrhea, sexual dysfunction, pathology of infertility and even a pituitary tumor.

Typical neuroleptics have a greater effect on dopamine receptors; Atypical same affect serotonin by other neurotransmitters (substances that transmit nerve impulses). Because of this, atypical neuroleptics rarely cause hyperprolactinaemia, extrapyramidal disorders, neuroleptic depression, as well as neurocognitive deficits and negative symptoms.

Signs of blockade of α ₁ -adrenoreceptors are lowering of arterial pressure, orthostatic hypotension, development of dizziness, and the appearance of drowsiness.

When H ₁ -gistamine receptors blockade, hypotension appears, the need for carbohydrates increases and body weight increases, as well as sedation.

If the blockade of acetylcholine receptors occurs, the following side effects occur: constipation, dry mouth, tachycardia, urinary retention, increased intraocular pressure, and accommodation disorders. There is also the possibility of confusion and drowsiness.

Western researchers have proved that between antipsychotics (new antipsychotics or old, typical or atypical - it does not matter) and sudden cardiac death is a link.

Also, the treatment with neuroleptics significantly increases the risk of stroke and myocardial infarction. This is because psychotic drugs affect lipid metabolism. Admission of neuroleptics can also trigger type 2 diabetes mellitus. The chances of getting serious complications increase with combined treatment with typical and atypical antipsychotics.

Typical antipsychotics can provoke epileptic seizures, since they lower the threshold of convulsive readiness.

Most antipsychotics (mainly phenothiazine antipsychotics) have a large hepatotoxic effect, and can even lead to the development of cholestatic jaundice.

Treatment of antipsychotics in the elderly can increase the risk of pneumonia by 60%.

Cognitive effect of antipsychotics

The conducted open studies showed that atypical neuroleptics are slightly more effective than those typical for the treatment of neurocognitive insufficiency. However, there is no convincing evidence of their at least some influence on neurocognitive impairment. Atypical antipsychotics, whose mechanism of action is slightly different from the typical ones, is often tested.

In one of the clinical studies, physicians compared the effects of risperidone and haloperidol in low doses. During the study, no significant differences in the indications were found. It was also proven that haloperidol in low doses positively affects neurocognitive indices.

Thus, the question of the effect of neuroleptics of the first or second generation on the cognitive sphere is still controversial.

Classification of antipsychotics

It has already been mentioned above that neuroleptics are divided into typical and atypical.

Among the typical neuroleptics can be identified:

1. Sedative antipsychotics (having a retarding effect after application): promazine, levomepromazine, chlorpromazine, alimamazine, chlorprotixen, pericyazin and others.
2. Induction antipsychotics (have a powerful global antipsychotic effect): fluphenazine, trifluoperazine, thioproperazine, pipotiazine, zuclopentixol, and haloperidol.
3. Disinhibitory (have an activating, disinhibiting action): carbidine, sulpiride and others.

Atypical antipsychotics include substances such as aripiprazole, sertindole, ziprasidone, amisulpride, quetiapine, risperidone, olanzapine and clozapine.

There is another classification of neuroleptics, according to which the following are distinguished:

1. Phenothiazines, as well as other tricyclic derivatives. Among them there are such types:
   
   ● Neuroleptics with a simple aliphatic bond (levomepromazine, alimamazine, promazine, chlorpromazine), powerfully block acetylcholine receptors and adrenoreceptors, have a pronounced sedative effect and are able to cause extrapyramidal disorders;
   ● Neuroleptics with a piperidine nucleus (thioridazine, pipotiazine, pericyazin), which have a moderate antipsychotic effect and poorly expressed neutocrine and extrapyramidal side effects;
   ● Neuroleptics with the piperazine core (fluphenazine, prochlorperazine, perphenazine, thioproperazine, frenolone, trifluoperazine), can block dopamine receptors, and also have little effect on acetylcholine and adrenoreceptors.
   
   
2. All derivatives of thioxanthene (chlorprotixen, flupentixol, zuclopentixol), whose action is similar to that of phenothiazines.
3. Substituted benzamides (tiaprid, sultopride, sulpiride, amisulpride), whose action is also similar to phenothiazine neuroleptics.
4. All derivatives of butyrophenone (trifluperidol, droperidol, haloperiodol, benperidol).
5. Dibenzodiazapine and its derivatives (olanzapine, clozapine, quetiapine).
6. Benzisoxazole and its derivatives (risperidone).
7. Benzisothiazolylpiperazine and its derivatives (ziprasidone).
8. Indole and its derivatives (sertindole, dicarbine).
9. Piperazinylquinolinone (aripiprazole).

Of all the above, it is possible to identify the available neuroleptics - drugs, without prescriptions being sold in pharmacies, and a group of antipsychotics that are sold strictly according to the doctor's prescription.

Interaction of antipsychotics with other drugs

Like any other medicines, modern antipsychotics interact with other drugs if taken simultaneously. Some interactions are very dangerous for the human body, so it is important to know what antipsychotics take dangerous. Remember that neuroleptic poisoning often occurs precisely because of their interactions with other drugs.

Interaction with antidepressants leads to an increase in the action of both antipsychotics and antidepressants themselves. Their combination can lead to constipation, paralytic intestinal obstruction, arterial hypertension.

It is not recommended to take together:

• The combination of neuroleptics and benzodiazepines leads to respiratory depression, sedative side effects.
• With simultaneous reception with lithium preparations, it is possible to develop hyperglycemia, the appearance of confusion, drowsiness. Their combination can be tolerated, but only with medical supervision.
• The use of adrenomimetics (ephedrine, metazone, norepinephrine, adrenaline) leads to a decrease in the effect of both drugs.
• Antihistamines with co-administration with neuroleptics increase their depressing effect on the central nervous system.
• The same effect is shared with antipsychotics, alcohol, anesthesia, hypnotics or anticonvulsants.
• The use of antipsychotics with analgesics and anesthetics leads to an increase in their effect. This combination depresses the central nervous system.
• Neuroleptics taken with insulin and antidiabetic drugs leads to a decrease in their effectiveness.
• When taking antipsychotics with tetracyclines, the risk of liver damage with toxins increases.

Contraindications

Both atypical and typical neuroleptics have a common list of contraindications:

• Individual intolerance to drugs;
• The presence of closed-angle glaucoma, prostate adenoma, porphyria, parkinsonism, pheochromocytoma;
• Allergic reactions to neuroleptics in a person's anamnesis;
• Disorders of the liver and kidneys;
• Pregnancy and lactation;
• Diseases of the cardiovascular system;
• Acute feverish conditions;
• coma.

Side Effects of Neuroleptics

With prolonged therapy, even the best neuroleptic exhibits side effects.

All antipsychotics may increase the risk of dopamine hypersensitivity, which in turn leads to symptoms of psychosis and tardive dyskinesia.

Most often, these symptoms appear when the neuroleptic is canceled (this is also called "withdrawal syndrome"). The withdrawal syndrome has several varieties: psychosis of hypersensitivity, unmasked dyskinesia (or dyskinesia of recoil), cholinergic "recoil" syndrome, etc.

To prevent this syndrome, treatment with neuroleptics must be completed gradually, gradually reducing the dose.

When taking antipsychotics in high doses, there is a side effect such as neuroleptic deficiency syndrome. According to unofficial data, this effect occurs in 80% of patients taking typical antipsychotics.

Structural changes in the brain with prolonged use

According to placebo-controlled studies of macaques, which for two years were given olanzapine or haloperidol in normal dosage, the volume and weight of the brain from taking antipsychotics decreases on average by 8-11%. This is due to the decrease in the volume of white and gray substances. Recovery after neuroleptics is impossible.

After the publication of the results, the researchers were accused of the fact that the action of neuroleptics was not tested on animals before being withdrawn to the pharmaceutical market, and that they pose a danger to humans.

One researcher, Nancy Andreasen, is confident that a decrease in the volume of gray matter and the administration of neuroleptics generally adversely affect the human body and leads to atrophy of the prefrontal cortex. On the other hand, she also noted that neuroleptics are an important medicine that can cure many ailments, but they need to be taken only in very small quantities.

In 2010, researchers J. Leo and J. Monricier published a survey of studies based on magnetic resonance images of the brain. The study was performed to compare the brain changes in patients taking antipsychotics and patients who did not take them.

In 14 of 26 cases (in patients taking antipsychotics), a decrease in brain volume, the volume of gray and white substances was observed.

Of 21 cases (in patients who did not take antipsychotics, or took, but in small doses) in no one was found any changes.

In 2011, the same researcher Nancy Andreasen published the results of a study in which she detected changes in the volume of the brain in 211 patients who took antipsychotics for a long time (more than 7 years). At the same time, the more the dose of drugs was, the greater the brain volume decreased.

Development of new drugs

At the moment, new neuroleptics are being developed that would not affect the receptors. One group of researchers stated that the antipsychotic effect has cannabidiol, a component of cannabis. So it is possible that soon we will see this substance on the shelves of pharmacies.

Conclusion

We hope that no one has any questions about what a neuroleptic is. What it is, what its mechanism of action and the consequences of the reception we have considered above. It only remains to add that, whatever the level of medicine in the modern world, no matter can be studied to the end. And a trick can be expected from anything, much less from such complex drugs as antipsychotics.

Recently, cases of treatment of depression with antipsychotics have become more frequent. Due to ignorance of the whole danger of this drug, people make themselves worse. Antipsychotics should in no case be used for any purpose other than their direct purpose. And about how the effect of these drugs produce on the brain, there is even no question.

That is why antipsychotics - drugs without prescriptions available for purchase, should be used with caution (and only if you are 100% sure that you need it), or even better not to apply at all without the appointment of a doctor.