New Antipsychotic Agents

While several potential antipsychotic agents are at various stages of development, two agents have gone through extensive testing, and new drug applications for these agents will likely soon be submitted to the FDA for approval. While one of these agents (iloperidone) has significant similarities to currently available second-generation antipsychotic agents, the other (aripiprazole) is the first agent of its type likely to become available. Other agents with distinct mechanisms of action are at earlier stages of assessment of antipsychotic efficacy.

Iloperidone. Iloperidone has gone through several clinical trials in a variety of conditions. In addition to the D2 and 5HT2A antagonism characteristic of currently available atypical agents, it is also a potent antagonist at the alpha-1 and alpha-2 noradrenergic receptors; the magnitude of this effect is comparable to that of clozapine. While its precise clinical profile needs further elucidation, studies thus far suggest that it is an "atypical" agent with potent antipsychotic activity and a low EPS liability (Jain, 2000).

Aripiprazole. Aripiprazole is a partial agonist at the dopamine D2 receptor, in contrast to existing antipsychotic agents, which are all full antagonists at the D2 receptor, albeit with different degrees of affinity for the receptor. In vivo, aripiprazole has been shown to exhibit antagonistic properties in animal models of dopaminergic hyper-activity and agonist activity in an animal model of dopamine hypoactivity. Aripiprazole has undergone extensive clinical testing, including studies comparing it to haloperidol and risperidone. It appears to be a potent antipsychotic with a low EPS liability (Carson et al., 2001). Although several D2 partial agonists have previously been evaluated for antipsychotic efficacy, none has reached the stage of development of aripiprazole, which is now available in the U.S.A.

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