Recent publications have drawn attention to the role of serotonin-2A receptors in mood disorders. Low doses of atypical antipsychotics, like the butyrophenone pipamperone, are suggested as an augmentation strategy in the antidepressant treatment of mood disorders, in addition to conventional antidepressant therapies.

Functional imaging studies with highly specific receptor ligands allow quick assessment of drug-receptor occupancy at different doses of drugs - here pipamperone at 5mg and 10mg doses - in a large animal model.

Three healthy drug-naïve female Beagle dogs, aged 7 years, were included.

Dogs were scanned before treatment and after administration of one dose of pipamperone of 5mg and 10 mg, 90 minutes prior to injection of the tracer. Acquisition was performed under general anaesthesia 90 minutes after injection of the tracer. The acquisition for both investigations was performed with a triple head gamma camera equipped with LEHR collimators. The images were reconstructed with HOSEM iterative reconstruction and application of a Butterworth-postfilter (cut-off 1,2 cycles/cm, order 8).

The mean binding serotonin-2A binding index before treatment in the frontal cortex was 1.47. In the 5 mg pre-treatment condition, the binding index was reduced to 1.29 and in the 10 mg pre-treatment condition, it was reduced to 1.04. Non-parametric statistics (Friedman related-samples test) yielded a p-value of 0.05.

Even in the very low dose range (5mg-10mg) of pipamperone, there was a significant and dose-dependent reduction in serotonin-2A binding index in the three dogs.