Mechanism of Action of Antipsychotic Agents

This video discusses the following topics:

• The dopamine hypothesis of schizophrenia (the evidence that supports it and its limitations).
• First Generation (typical) antipsychotics are D2 antagonists.
• Pharmacodynamic profile of second generation antipsychotics (5-HT2A antagonism, fast D2 dissociation, 5-HT1A agonism).
• The main differences between first and second generation antipsychotics (from a receptor binding perspective).

References and further reading

• Brunton LB, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2010.
• Stahl, S M. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York: Cambrigde University Press; 2008
• Meltzer HY, Matsubara S, Lee JC. The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull. 1989;25(3):390-2.
• Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry. 2001;158(3):360-9.