Antipsychotic Drugs: Typical and Atypical Agents

Antipsychotic drugs can be categorized as first-generation or typical and second-generation or atypical agents.

All antipsychotic drugs act by inhibiting dopamine receptors, although the extent of this inhibition varies significantly among different drugs.

Typical antipsychotics like chlorpromazine and haloperidol primarily target D₂ receptors in the brain.

Clinical efficiency typically corresponds to receptor occupancy ranging from 60 to 75%. However, receptor occupancy exceeding 78% can lead to extrapyramidal side effects.

In contrast, atypical agents such as risperidone and lurasidone block both D₂ receptors and 5HT_2A receptors.

These agents are also partial 5HT_1A receptor agonists, producing anxiolytic effects.

Drugs like clozapine and risperidone additionally show varying degrees of α₂ adrenoceptor antagonism.

Antipsychotics are generally lipophilic, resulting in their distribution and accumulation in well-vascularized tissues, including the brain.

They can also cross into fetal circulation and breast milk, posing potential risks during pregnancy and lactation.