Conventional antipsychotic drugs, also known as “typical antipsychotics,” are the first generation of medications developed in the 1950s to treat psychosis. Their discovery was a turning point in psychiatry, offering a treatment for symptoms like hallucinations and delusions. Before these drugs, treatment options for severe mental illness were limited. Their development changed the approach to mental healthcare, allowing many individuals to receive treatment in community settings instead of long-term institutions.
Mechanism of Action in the Brain
The primary action of conventional antipsychotics is linked to the neurotransmitter dopamine. Psychosis is often explained by the “dopamine hypothesis,” which suggests that an overactivity of dopamine contributes to psychotic symptoms. Conventional antipsychotics function as dopamine D2 receptor antagonists, meaning they bind to and block D2 receptors on nerve cells. This action prevents dopamine from exerting its effects.
This blocking action is most pronounced in the brain’s mesolimbic pathway, an area associated with reward and motivation. Reducing dopamine activity here is thought to alleviate positive symptoms like hallucinations. To visualize this, the dopamine receptor is like a lock and dopamine is the key. A conventional antipsychotic drug acts like a faulty key that gets stuck in the lock, preventing the correct dopamine key from entering and transmitting a signal.
By occupying these D2 receptors, the drugs lower the volume on excessive dopamine signaling. Brain imaging studies show that blocking about 60-75% of D2 receptors is associated with the desired antipsychotic effect. This targeted reduction in dopamine transmission is the mechanism through which these medications stabilize brain function.
Conditions Treated and Drug Examples
Conventional antipsychotics are prescribed for psychiatric conditions characterized by psychosis. Their most prominent use is managing schizophrenia, where they reduce “positive” symptoms like hallucinations, delusions, and disordered thinking. These medications help restore a connection to reality for individuals experiencing these symptoms.
Beyond schizophrenia, these drugs treat the manic phase of bipolar disorder, which can be accompanied by psychotic features like grandiosity or paranoia. They are also indicated for other psychotic disorders and severe agitation. Common examples of conventional antipsychotics include:
- Chlorpromazine
- Haloperidol
- Fluphenazine
- Loxapine
Characteristic Side Effects
Conventional antipsychotics are known for causing movement-related side effects, which result from their mechanism of blocking dopamine receptors. These effects are grouped under the term extrapyramidal symptoms (EPS) and can manifest in several ways. The primary types of EPS and other major side effects include:
- Acute dystonia: Sudden, involuntary muscle spasms, often in the neck, jaw, or eyes.
- Akathisia: An intense inner feeling of restlessness that compels constant motion, like pacing.
- Parkinsonism: Symptoms that mimic Parkinson’s disease, including tremor, muscle rigidity, and slow movement.
- Tardive dyskinesia (TD): A potentially irreversible disorder from long-term use, causing involuntary movements like lip-smacking or tongue thrusting.
- Neuroleptic malignant syndrome (NMS): A rare but life-threatening reaction with high fever, severe muscle rigidity, and confusion.
- Other effects: Sedation and a drop in blood pressure upon standing (orthostatic hypotension).
Comparison with Atypical Antipsychotics
A newer class of drugs, known as atypical or second-generation antipsychotics, provides an alternative to conventional medications. The primary distinction between the two classes is their side effect profiles and mechanism of action. This contrast creates different risk-benefit calculations for treatment.
Conventional antipsychotics primarily block dopamine D2 receptors, while atypical antipsychotics affect both dopamine and serotonin receptors. This broader mechanism may contribute to their effectiveness for “negative” symptoms of schizophrenia, such as apathy and social withdrawal. Conventional drugs do not address these symptoms as effectively.
The primary difference is the side effect profile. Conventional antipsychotics carry a high risk of movement disorders like EPS and tardive dyskinesia. Atypical antipsychotics have a lower risk of these issues but are associated with a higher risk of metabolic side effects. These include significant weight gain, an increased risk of type 2 diabetes, and high cholesterol. This trade-off is a central factor in selecting an antipsychotic medication.