The straight dopa
How Pierre Fabre plans to avoid pitfalls with D3 antagonist in schizophrenia
Laboratoires Pierre Fabre S.A. thinks the dopamine D3 receptor hypothesis of schizophrenia hasn't been fully tested yet because the compounds that failed earlier trials didn't engage enough of the receptors. To avoid that problem, the company developed new screening protocols and new chemistry, and conducted PET studies to show receptor occupancy prior to beginning a Phase IIa study of F17464 early this month.
Most antidopaminergic antipsychotics reduce the activity of both dopamine D2 and D3 receptors. It has been postulated that the D3 receptor alone is responsible for the drugs' ability to quell positive schizophrenia symptoms such as delusions and hallucinations, while D2 is responsible for deleterious effects these agents have on cognition and negative symptoms such as social withdrawal.
Finding a compound that can test this hypothesis has proved challenging because D2 receptors are about 4-5 times more abundant in the brain than