Reply to A Different Mechanism to Understand Activation/Sedation Side Effects of Ziprasidone

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Sir:‘ ‹ When the mechanism of action of psychotropic drugs can successfully explain their clinical actions, this generally means that the best of the science of receptor pharmacology has been thoughtfully combined with the best of the art of clinical observation. Mr. Shayegan and I reviewed the receptor binding properties of ziprasidone¹ and all atypical antipsychotics² and provided hypotheses about which receptor binding actions were common to all atypical antipsychotics, which were unique for some agents and not others, and, finally, which receptor binding properties could feasibly be related to efficacy versus side effects of the various drugs in this class. Brophy has used this approach in an attempt to explain his clinical observations of motor restlessness with ziprasidone and hypothesizes that the serotonin-1B (5-HT_1B) actions of ziprasidone, but not the 5-HT_2C actions that we propose to account for behavioral activation of ziprasidone, may account for these observations.’ ‹