Radioligand binding studies were used to analyze the interactions of two novel anxiolytics,
buspirone and TVX Q 7821, with a series of 10 neuronal membrane receptor sites. Buspirone
(IC50 = 24 nM) and TVX Q 7821 (IC50 = 9.5 nM) display the highest affinity for 5-hydroxytryptamine1A
(5-HT1A) binding sites labeled by 3H-8-hydroxy-2-(di-n-pro-pylamino) tetralin (DPAT).
By contrast, buspirone is 16-fold weaker at dopamine (D2) receptors (IC50 = 380 nM),
whereas TVX Q 7821 is 6-fold less potent at alpha-adrenergic1 sites (IC50 = 58 nM).
At the other receptors studied, buspirone and TVX Q 7821 had similar pharmacological
profiles. Both agents display moderate affinity for histamine (H1), alpha-adrenergic2,
and 5-HT2 binding sites. The drugs are essentially inactive at 5-HT1B, calcium channel
antagonist, muscarinic cholinergic, and benzodiazepine receptors. These results suggest
that the anxiolytic effects of buspirone and TVX Q 7821 may be mediated by central