Ziprasidone May Have Unique Neuroleptic Activity

Pfizer's ziprasidone will probably come to market somewhat later than other compounds among the new generation of atypical antipsychotics, but the company believes it has a pharmacological profile which could distinguish it from its competitors. An update on the drug's progress was given at the Collegium Internationale Neuropsychopharmacologicum on June 24.

Like other new schizophrenia drugs, ziprasidone reflects the movement away from the dominance of dopamine D2 receptor blockade as the major target for drug treatment. There is a growing body of evidence which suggests that the D2 receptor hypothesis is far from the whole story for schizophrenia, not least the fact that one of the most effective drugs in the disease, Sandoz' Clozaril (clozapine), has very modest D2 receptor occupancy.

It is now thought that the serotonin 5-HT2 receptor subtypes may be important targets in schizophrenia, and the new generation of drugs are all relatively more potent 5-HT2A antagonists than dopamine D2 antagonists. "Ziprasidone has one of the highest serotonin 5-HT2A/dopamine D2 affinity ratios among the new antipsychotics in clinical development," according to Herbert Meltzer of Case Western University School of Medicine.