Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors.
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 5-HT1A receptors.
Peroutka
S J
SJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D002065:Buspirone; D002417:Cattle; D003864:Depression, Chemical; D003975:Diazepam / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D066298:In Vitro Techniques; D008140:Lorazepam / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D005445:Flunitrazepam; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008140:Lorazepam; D003975:Diazepam; D002065:Buspirone