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 5HT(2) receptor antagonists such as ketanserin and risperidone or DA D-2 receptor antagonis ts such as haloperidol and raclopride, the effect of ritanserin proved to b e more potent. Ritanserin blocked the DA transporter with a K-i of 0.18 +/- 0.06 muM, similar to cocaine (0.11 +/- 0.005 muM), while ketanserin had a K-i 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 loca l application to the synaptosomes, ritanserin potently released [(3)]H-DA l eaving only 29.6 +/- 1.6% of DA content, while ketanserin effect was equal to 46.5 +/- 0.9%; haloperidol to 70.4 +/- 2.2% and risperidone to 73.9 +/- 1.5%, all tested at the dose of 10 muM. 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 n egative symptoms of schizophrenia.