Pharmacology · Class
Second-generation antipsychotics !
The «atypical» antipsychotics: fewer movement side effects than the older drugs, but several cause weight gain, diabetes and high lipids.
Updated 2026-11-01
What they are
Antipsychotics that combine D2 blockade (or partial agonism, as with aripiprazole) with strong 5-HT2A blockade. They treat schizophrenia and bipolar mania, and some have further uses (bipolar depression, irritability in autism, Tourette's disorder). Clozapine is the reference drug for treatment-resistant schizophrenia.
Mechanism of action
Blocking 5-HT2A receptors increases dopamine release in the striatum and cortex, so they cause fewer extrapyramidal effects at doses that still block mesolimbic D2. Their H1, 5-HT2C, α1 and muscarinic actions differ from drug to drug and explain sedation, weight gain and hypotension.
Target: Dopamine D2 and serotonin 5-HT2A receptors
Drugs in this class
- ClozapineThe most effective antipsychotic for treatment-resistant schizophrenia; it can cause severe neutropenia, so blood…Dopamine D2 receptor
- OlanzapineAn atypical antipsychotic for schizophrenia and bipolar mania; effective but with one of the highest risks of weight…Dopamine D2 receptor
- QuetiapineA sedating atypical antipsychotic for schizophrenia and for both manic and depressive phases of bipolar disorder; few…Dopamine D2 receptor
- RisperidoneAn atypical antipsychotic for schizophrenia, bipolar mania and irritability in autism; the atypical that raises…Dopamine D2 receptor
- AripiprazoleAn atypical antipsychotic that is a partial agonist at D2: little prolactin rise and lower metabolic risk, but…Dopamine D2 receptor (partial agonist); serotonin 5-HT1A receptor shown
Others in the class
- Paliperidone
- Ziprasidone
- Lurasidone
- Asenapine
- Cariprazine
- Brexpiprazole
Test yourself
Think of the answer, then tap the question to see it.
Which receptor action is thought to explain the lower rate of extrapyramidal effects of atypical antipsychotics?
Strong 5-HT2A blockade, which increases striatal dopamine release and offsets part of the D2 blockade there.
Which two atypical antipsychotics carry the highest risk of weight gain and diabetes?
Clozapine and olanzapine.
Which atypical antipsychotic is most associated with high prolactin?
Risperidone (and its active metabolite).
What blood test is essential during clozapine treatment, and why?
The absolute neutrophil count, because clozapine can cause severe neutropenia with life-threatening infections.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - CLOZAPINE tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - OLANZAPINE tablet (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 19 (McGraw Hill, 2023).
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Representative model, for educational purposes only.