The 5-HT2 antagonist ritanserin blocks dopamine re-uptake in the rat frontal cortex

The effect of ritanserin on dopamine (DA) re-uptake and efflux was studied in rat frontal cortex synaptosomes. When compared to other 5HT2 receptor antagonists such as ketanserin and risperidone or BA D2 receptor antagonists such as haloperidel and raclopride, the effect of ritanserin proved to be more potent. Ritanserin blocked the DA transporter with e K1 of 0.18 ± 0.06 μM, similar to cocaine (0.11 ± 0.005 μM), while ketanserin had a K1 of 0.93 ± 0.045; haloperidol of 2.07 ± 0.12; risperidone of 18.01 ± 0.62 and raclopride of 24.01 ± 1.55. In addition, 15 min from its local application to the synaptosomes, ritanserin potently released [3]H-DA leaving only 29.6 ± 1.6% of DA content, while ketanserin effect was equal to 45.5 ± 0.9%; haloperidol to 70.4 ± 2.2% and risperidone to 73.9 ± 1.5%, all tested at the dose of 10 μM. Cocaine had no effect on DA efflux. These results suggest that ritanserin has a intrinsic dopaminergic effect which may help to explain its reported improvement on mood, cognition and negative symptoms of schizophrenia.