3H-TVX Q 7821: identification of 5-HT1 binding sites as target for a novel putative anxiolytic

In order to clarify the mechanism of action of the putative nonbenzodiazepine anxiolytic TVX Q 7821 [2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1, 2-benzisothiazol-3-(2H)one-1,1-dioxidehydrochloride], binding studies with the radio labelled compound were performed. 3H-TVX Q 7821 bound rapidly, reversibly and in a saturable manner with high affinity to calf brain structures with preference for the hippocampus (KD 1.62 nmol/l; Bmax 320 fmol/ mg protein). 3H-TVX Q 7821 binding was displaced only by 5-hydroxytryptamine and its agonists and antagonists including spiperone, but was not displaced by a variety of other neurotransmitters and drugs. The 5-HT2 receptor antagonist ketanserin was a weak displacer. The hippocampal binding sites for 3H-TVX Q 7821 were pharmacologically very similar to the 5-HT1-binding sites in this region. TVX Q 7821 is likely to be an important tool in research on functional aspects of 5-HT1 binding sites.