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The Neuroscientist
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Activation is Hallucinogenic and Antagonism is Therapeutic: Role of 5-HT2A Receptors in Atypical Antipsychotic Drug Actions

Bryan L. Roth

Departments of Psychiatry, Biochemistry and Neurosciences Case Western Reserve University Medical School Cleveland, Ohio

David L. Willins

Department of Biochemistry, Case Western Reserve University Medical School Cleveland, Ohio

Kurt Kristiansen

Department of Biochemistry, Case Western Reserve University Medical School Cleveland, Ohio

Wesley K. Kroeze

Department of Biochemistry, Case Western Reserve University Medical School Cleveland, Ohio

This review summarizes recent studies with 5-hydroxytryptamine2A (5-HT2A) receptors, which represent the major site of action of hallucinogens and a likely site for atypical antipsychotic drug actions. We present evidence demonstrating that atypical antipsychotic drugs, as a group, have a preferentially high affinity for 5-HT2A receptors, compared with their affinities for other neurotransmitter receptors. The 5-HT2A receptor blockade seen with atypical antipsychotic drugs is probably an essential factor in explaining many of the unique features of atypical antipsychotic drugs. Atypical antipsychotic drugs have high affinities for several other 5-HT receptors (5-HT2C, 5-HT6, and 5-HT7), and the potential role of these novel 5-HT receptors in atypical antipsychotic drug action is also summarized.

Key Words: KEY WORDS Atypical antipsychotic drugs • Clozapme • 5-HT2A receptors • Serotonin

The Neuroscientist, Vol. 5, No. 4, 254-262 (1999)
DOI: 10.1177/107385849900500414
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