How Do First-Generation Antipsychotics Work?

Reviewed on 12/30/2022

How Do First Generation Antipsychotics Work and Function?

First-generation antipsychotics are medications used in the treatment of schizophrenia and psychosis. First-generation antipsychotics, also known as typical or conventional antipsychotics are the initial class of drugs developed to treat psychotic disorders.

First-generation antipsychotics primarily work by reducing the activity of dopamine, one of the chemicals (neurotransmitters) released in the brain by nerve cells (neurons) to transmit signals. Some of the first-generation antipsychotics also have effects on other neurotransmitters such as norepinephrine and acetylcholine.

  • Dopamine has many functions, including pleasure sensation, mood, learning, and memory.
  • Norepinephrine improves energy and attention.
  • Acetylcholine is responsible for muscle contraction and treats nervous system disorders that cause uncontrolled muscle contractions. 

First-generation antipsychotics work by blocking D2 dopamine receptors, protein molecules on neuronal membranes that initiate excitatory action when stimulated by dopamine. The first-generation antipsychotics also depress the release of hormones by the hypothalamus and pituitary gland.

One of the first-generation antipsychotics, loxapine, in addition to D2 receptors, blocks the activity of serotonin 5-HT2A receptors.  Serotonin is another neurotransmitter that regulates mood and behavior, blocks 5-HT2A receptors which are excitatory, reduces aggression, and has a calming effect.

How Are First Generation Antipsychotics Used?

First-generation antipsychotics may be administered as:

  • Oral tablets, capsules, solutions, or oral inhalations
  • Intramuscular (IM), intravenous (IV), or subcutaneous (SC) injections

First-generation antipsychotics are used to treat the following conditions:


  • Psychotic disorders
  • Schizophrenia
  • Sedation for psychosis
  • Acute agitation
  • Behavioral disorders
  • Schizophrenia and bipolar I agitation
  • Non-psychotic anxiety
  • Tourette syndrome (a nervous system disorder involving repetitive movements or unwanted sounds)
  • Nausea and vomiting

Off-label uses:

What Are Side Effects of First Generation Antipsychotics?

Side effects of first-generation antipsychotics may include the following:

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

What Are Names of Some First Generation Antipsychotic Drugs?

Generic and brand names of first-generation antipsychotic drugs include:


Health Solutions From Our Sponsors