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.
Dompert
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Glaser
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Traber
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001665:Binding Sites; D002417:Cattle; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011619:Psychotropic Drugs / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D014316:Tritium
D014151:Anti-Anxiety Agents; D018377:Neurotransmitter Agents; D011619:Psychotropic Drugs; D011743:Pyrimidines; D011985:Receptors, Serotonin; D014316:Tritium; C043077:ipsapirone