How Do Second Generation Antipsychotics Work?

Reviewed on 3/24/2022

How Do Second Generation Antipsychotics Work?

Second generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic medications used to treat schizophrenia, bipolar disorder and related psychiatric conditions. Second generation antipsychotics were developed to improve upon the efficacy and safety of first generation antipsychotics (FGAs).

Second generation antipsychotics work by blocking the excitatory activity of dopamine and serotonin, chemicals (neurotransmitters) released by nerve cells (neurons) to transmit nerve signals. Dopamine and serotonin regulate many functions including pleasure sensation, mood, behavior, learning and memory, among others.

While most FGAs block only D2 dopamine receptors, SGAs block both D2 receptors and 5-HT2A serotonin receptors. Receptors are protein molecules on the surface of neurons that initiate action when stimulated by these neurotransmitters. D2 and 5-HT2A receptors are types of excitatory receptors, believed to be involved in psychosis.

Some SGAs work by also stimulating 5-HT1 serotonin receptors, which are inhibitory receptors, in addition to blocking 5-HT2A receptors. SGAs also have effects on other neurotransmitters such as norepinephrine.

Second generation antipsychotics have a lower risk for neurological movement disorders known as extrapyramidal symptoms, which are the most common side effects associated with FGAs. SGAs, however, are associated with a higher risk for metabolic side effects such as weight gain, increase in blood glucose and cholesterol levels.

Both FGAs and SGAs are effective for the treatment of schizophrenia’s positive symptoms such as hallucinations and delusions. However, there is no evidence that SGAs have more efficacy than FGAs in alleviating cognitive and negative symptoms such as apathy and social withdrawal.

How Are Second Generation Antipsychotics Used?

Second generation antipsychotics may be administered as:

  • Oral: Tablets, capsules, solutions, suspensions, or sublingual tablets (placed under the tongue)
  • Transdermal: Skin patches
  • Injections: Intramuscular or subcutaneous

Second generation antipsychotics are used to treat the following conditions:


Off-label uses:

Orphan designation:

  • N-glycanase 1 (NGLY1) deficiency


Schizophrenia is the most disabling mental illness. See Answer

What Are Side Effects of Second Generation Antipsychotics?

Side effects of second 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 Second Generation Antipsychotic Drugs?

Generic and brand names of second generation antipsychotic drugs include:


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