Effects of 5HT uptake inhibitors on the pressor response to 5HT in the pithed rat. The significance of the 5HT blocking property.

A study was made of the effects of several serotonin (5HT) uptake inhibitors on 5HT-induced pressor responses in pithed rats, 5HT uptake into rat brain synaptosomes and 5HT-induced contractions of rat ileum in vitro. All drugs except desimipramine were potent uptake inhibitors (IC50 less than 10(-7) M), Femoxetine, chlorimipramine, imipramine and desimipramine all inhibited 5HY-induced contractions of the rat ileum in vitro and the pressor response to 5HT in vivo. FG 7051, FG 7052 and dexchlorpheniramine were weak 5HT antagonists on the rat ileum but potentiated the pressor responses to 5HT; the most potent uptake inhibitor, FG 7051, was the strongest potentiator. These results suggest that uptake inhibition is important for this potentiation. It is concluded that 5HT uptake inhibitors with potent 5HT receptor blocking properties antagonize the pressor response to 5HT and mask the potentiation due to uptake inhibition.