Serotonin Receptors Involved In Antipsychotic Drug Action
The
hypothesis that a relatively high affinity for the 5-HT2A receptor compared to
an affinity for the D2 receptor was the basis for the difference between
atypical and typical antipsychotic agents contributed to the development of the
newer antipsychotic agents listed above, all of which support the previously
mentioned hypothesis of high affinity for 5-HT2A and low affinity for D2
receptors.
However, other 5-HT receptors may be important to the action of
clozapine and other recently introduced antipsychotic agents, or of potential
value for developing more effective or better tolerated antipsychotic agents.
These
include the 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptors. Although
some of the atypical antipsychotic drugs developed on the basis of the
5-HT2A/D2 hypothesis also have affinities for 5-HT2C, 5-HT3, 5-HT6, or 5-HT7
receptors that are in the same range as that for the 5-HT2A receptor, this is
not characteristic of all of these agents, and thus it is not likely that
affinities for these receptors are primary factors contributing to the low EPS
profile of the entire class of agents.
However,
this does not rule out that actions at various 5-HT receptors contribute to low
EPSs of specific drugs, or other actions, e.g., cognitive improvement or
improvement in negative symptoms. For example, 5-HT1A receptor agonism has also
been suggested to be able to contribute to an atypical antipsychotic drug
profile, and some of the atypical antipsychotics are 5-HT1A partial agonists as
well as 5-HT2A/5-HT2C antagonists, e.g., clozapine, quetiapine, ziprasidone,
and S16924. The role of the 5-HT4 receptor in cognition will be discussed
subsequently. Furthermore, there is some evidence of interactions among the
5-HT1A, 5-HT2A, and 5-HT2C receptors. Because of space limitations, this
chapter focuses on these three 5-HT receptors and briefly considers the others.
(Ichikawa et al., 2000)
Table: Mechanisms of action of antipsychotics
