(Z)‐Dimethylamino‐l‐(4‐bromophenyl)‐l‐(3‐pyridyl) propene (H 102/09), a New Selective Inhibitor of the Neuronal 5‐Hydroxytryptamine Uptake

Abstract

Abstract The inhibition of the uptake of 3 H–(–)–noradrenaline (NA), 3 H–dopamine and 14 C–5–hydroxytryptamine (5–HT) in mouse brain slices by (Z)–3–dimethylamino–l–(4–bromophenyl)–l–(3–pyridyl)propene (H 102/09), desipramine and chlorimipramine and their releasing effect on the 3 H–amines previously accumulated in the slices were examined. The interactions with reserpine produced hypothermia and sedation and the 5–hydroxytryptophan (5–HTP) syndrome in mice were also studied. Due to the poor inhibitory activity on the NA uptake H 102/09 was a more selective inhibitor of the 5–HT uptake than was chlorimipramine, particularly after administration in vivo, where it was as potent as chlorimipramine (ED50 = 19 μmol/kg intraperitoneally). In vitro chlorimipramine was 6 to 12 times more active than H 102/09. Desipramine was a very selective inhibitor of the NA uptake in vitro and in vivo. The compounds were generally more potent in inhibiting the uptake than in releasing the amines. However, in striatal slices the inhibition of DA uptake could be due to the releasing effect since the difference in potencies were small. The effect of desipramine on 5–HT uptake and that of H 102/09 on NA uptake could also involve a release component. The 5–HTP syndrome was potentiated by H 102/09 and chlorimipramine but not by desipramine. The reserpine hypothermia but not the sedation was potently antagonized and reversed by desipramine and by chlorimipramine at high doses but not by H 102/09, suggesting that NA but not 5–HT is involved in the hypothermic action of reserpine.