Effect of a specific 5-HT uptake inhibitor, citalopram (Lu 10-171), on 3H-5-HT uptake in rat brain synaptosomes in vitro.

The uptake of 3H-5-HT in synaptosomes from rat brains was investigated. Addition of DA or NA had only a slight or no effect on the uptake. When the uptake into NA and DA neurons was inhibited by the addition of high concentrations of NA and DA, the uptake of 3H-5-HT was unchanged. This was also found after destruction of NA and DA neurons by 6-hydroxydopamine treatment. Furthermore, the uptake of 3H-5-HT was almost equal in different brain parts containing NA and DA in very different amounts. These observations show that the uptake measured with 3H-5-HT is specific for 5-HT neurons. The present study revealed that citalopram and chlorimipramine inhibited uptake competitively, and in this respect the two drugs were equipotent. Compared with a series of tricyclic thymoleptics, the two drugs were the most potent inhibitors of 5-HT uptake, about 20 to 35 times more active than imipramine and amitriptyline. The metabolites of citalopram were also rather potent. The results obtained in the present study correlate closely with those obtained using inhibition of 14C-5-HT uptake in blood platelets, or using the inhibition of H 75/12-induced 5-HT depletion in rat brain. When rats were treated orally with citalopram or chlorimipramine, the inhibition of 3H-5-HT uptake in synaptosomes derived from these rats was two times greater after citalopram than after chlorimipramine.