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.
Mamo
David
D
Department of Psychiatry, University of Toronto, Toronto, Canada.
Sedman
Ewen
E
Tillner
Joachim
J
Sellers
Edward M
EM
Romach
Myroslava K
MK
Kapur
Shitij
S
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005462:Fluorine Radioisotopes; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011744:Pyrimidinones; D019275:Radiopharmaceuticals; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists
C484815:EMD 281014; D005462:Fluorine Radioisotopes; D007211:Indoles; D010879:Piperazines; D011744:Pyrimidinones; D019275:Radiopharmaceuticals; D044348:Receptors, Serotonin, 5-HT2; D058830:Serotonin 5-HT2 Receptor Antagonists; C045359:setoperone