EMD 281014, a specific and potent 5HT2 antagonist in humans: a dose-finding PET study.

While serotonin 5HT2-receptors have been implicated in the etiology and pharmacological treatment of a number of neuropsychiatric conditions, there are few potent and specific agents available for use in human clinical studies. EMD 281014 is a highly specific 5HT2-receptor antagonist that is currently under development. To find optimal doses for early clinical studies, we conducted a PET study using [18F]setoperone in nine healthy subjects scanned at baseline and following the administration of 1, 3, and 7 mg EMD 281014. The study drug was well tolerated by all study participants, and all doses resulted in > or =70% occupancy at frontal 5HT2-receptors 3 h after drug administration. The data suggest that daily dosing of > or =3 mg EMD 281014 should be sufficient to provide sustained high levels of 5HT2-receptor occupancy in future clinical trials.