Classification of antipsychotics
Drugs in this category are divided into two major groups depending on their mechanism of action and profile of potential adverse reactions:
- "Typical" antipsychotics: classical representatives of the group, including haloperidol, chlorpromazine (aminazine), fluphenazine, droperidol, thioridazine, and chlorprothixene.
- "Atypical" antipsychotics: modern agents, which include clozapine, risperidone, olanzapine, and aripiprazole.
Pharmacological profile of typical neuroleptics
Traditional agents exhibit strong antipsychotic effects and a pronounced antiemetic effect. In addition, they are capable of potentiating (i.e., enhancing) the action of general anesthetics and opioid analgesics.
The main feature of typical agents is a high risk of developing extrapyramidal disorders (parkinsonism, dystonia, dyskinesia), which serve as a marker for this group (especially pronounced with haloperidol and chlorpromazine). They also cause endocrine disorders in the form of hyperprolactinemia, which can manifest as galactorrhea.
Features of chlorpromazine (Aminazine)
Chlorpromazine occupies a special place among typical neuroleptics due to its pharmacological properties:
- It exhibits pronounced M-anticholinergic activity, which distinguishes it from haloperidol, in which this effect is less pronounced.
- It affects the autonomic nervous system through adrenolytic and anticholinergic actions.
- It can cause galactorrhea due to elevated prolactin levels.
- In terms of antipsychotic potency, it is inferior to haloperidol.
Features of atypical antipsychotics
The main difference of atypical agents (olanzapine, aripiprazole, clozapine) is that extrapyramidal symptoms are not typical for them when used at therapeutic doses.
Unlike classical typical agents, these drugs demonstrate higher efficacy regarding the "negative" symptoms of psychoses, such as social withdrawal and apathy.
Briefly: answers to topical questions
What is the molecular mechanism of the antipsychotic action of typical neuroleptics?
The molecular mechanism of the antipsychotic action of typical neuroleptics consists of the blockade of postsynaptic dopamine $D_2$ receptors in the central nervous system. The main site of action is the mesolimbic pathway of the brain. Due to this mechanism, the drugs alleviate primarily the positive symptoms of psychosis, such as delusions and hallucinations. At the same time, they have virtually no effect on negative symptoms and cognitive impairment.
What is the pathogenetic mechanism of hyperprolactinemia development during the administration of typical neuroleptics?
The pathogenetic mechanism of hyperprolactinemia development is due to the blockade of dopamine $D_2$ receptors in the tuberoinfundibular pathway, which includes the hypothalamus and pituitary gland. Normally, dopamine acts as a prolactin-inhibiting factor. Blockade of receptors by typical neuroleptics eliminates this physiological inhibitory effect on the anterior pituitary, leading to increased prolactin secretion. Clinically, this endocrine disorder can manifest as galactorrhea in women, gynecomastia in men, and a decrease in gonadotropin production resulting in amenorrhea and impotence.
Which receptors are predominantly blocked by atypical neuroleptics?
Atypical neuroleptics predominantly block serotonin 5-HT₂A and dopamine D₂ receptors. They are characterized by a high ratio of 5-HT₂A receptor blockade to D₂ receptor blockade. The receptor profile also includes blockade of α-adrenergic receptors and H₁-histamine receptors; there is practically no effect on m-cholinergic receptors. The blockade of 5-HT₂A receptors reciprocally increases dopaminergic activity in the nigrostriatal system, which compensates for D₂ receptor blockade and reduces the risk of extrapyramidal symptoms.
What is the mechanism of the antiemetic action of typical neuroleptics?
The mechanism of the antiemetic action of typical neuroleptics is due to the blockade of dopamine $D_2$ receptors located in the chemoreceptor trigger zone of the vomiting center. This chemoreceptor zone is located on the floor of the fourth ventricle of the medulla oblongata and is not protected by the blood-brain barrier. By inhibiting $D_2$ receptors in this area, typical antipsychotics block the transmission of impulses arising in response to the action of chemicals in the blood or cerebrospinal fluid, thereby suppressing the vomiting reflex.
Typical agents are "troublesome" regarding the extrapyramidal system (cause extrapyramidal symptoms), while atypical ones are "neat" (without these side effects at therapeutic doses).
Class and exam questions
What is the main difference between typical and atypical neuroleptics?
Typical neuroleptics have a high risk of developing extrapyramidal symptoms (parkinsonism, dystonia) at therapeutic doses, whereas this phenomenon is not typical for atypical drugs.
Which drug is stronger in antipsychotic potency: haloperidol or chlorpromazine?
Haloperidol surpasses chlorpromazine in antipsychotic potency. In addition, chlorpromazine has more pronounced M-anticholinergic activity.
Why do typical neuroleptics cause galactorrhea?
Galactorrhea occurs due to the development of hyperprolactinemia — an endocrine disorder caused by the action of drugs in this group.
What else to study on this topic
- Detailed receptor profile of chlorpromazine and its effect on the autonomic nervous system
- Comparison of the severity of the antiemetic effect among various representatives of typical neuroleptics
- Mechanisms of hyperprolactinemia development and clinical manifestations of endocrine disorders
- Pharmacodynamics of atypical antipsychotics (olanzapine, aripiprazole, clozapine) regarding negative symptoms
- Potentiation of general anesthetics and opioid analgesics by typical neuroleptics
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