Schizophrenia, bipolar mood disorder, significant irritability, and aggression
Mechanisms of Action
There has been considerable debate about the difference between the traditional antipsychotics and the so-called atypicals. Indeed, the matter is not completely settled. It is generally agreed that the traditional antipsychotics exert their beneficial and adverse effects through dopamine blockade at the dopamine D2 receptor. The traditional antipsychotic, haloperidol, is a potent blocker of dopamine. Its capacity to bind to D2 receptors is strong, and it is not easily displaced by dopamine in the brain. This affinity and persistent binding to D2 receptors in the basal ganglia probably accounts for the motor side effects described above. By contrast, clozapine (often considered the prototype atypical) has much lower affinity for D2 receptors. Across the current list of atypical antipsychotics, the affinity for D2 receptors varies. For example, risperidone has strong affinity for D2 receptors – but it does not appear to have the same firm hold on these receptors as haloperidol does. Because the hold on the D2 receptors is not firm, endogenous dopamine is more able to bind to the receptors, and we are less likely to see the motor side effects associated with haloperidol.
Specific Compounds and Properties
Antipsychotic medications are a large group of medications developed primarily for the treatment of schizophrenia. The antipsychotic medications were introduced in the 1950s with so-called second-generation antipsychotics appearing in the 1990s. These newer medications have properties in common with the older antipsychotics but also important differences.
Because of the adverse neurological effects of the traditional antipsychotic medications, chemists looked for new compounds that would maintain the antipsychotic benefits with decreased risk of neurological side effects. This led to the introduction of the so-called atypical antipsychotics. These medications include clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, asenapine, iloperidone, and lurasidone. As a class, these atypical antipsychotics, also called second-generation antipsychotics, do indeed reduce the risk of neurological adverse effects. However, depending on the actual drug discussed, they have varying degrees of risk for other adverse effects.
References and Reading
- Martin, A., Scahil, L., & Christopher, K. (2010). Pediatric psychopharmacology: Principles and practice (2nd ed.). New York: Oxford.Google Scholar