Author/Authors :
Andreas Kling، نويسنده , , Udo E.W. Lange، نويسنده , , Helmut Mack، نويسنده , , Margot H.M. Bakker، نويسنده , , Karla U. Drescher، نويسنده , , Wilfried Hornberger، نويسنده , , Charles W. Hutchins، نويسنده , , Achim M?ller، نويسنده , , Reinhold Müller، نويسنده , , Martin Schmidt، نويسنده , , Liliane Unger، نويسنده , , Karsten Wicke، نويسنده , , Kurt Schellhaas، نويسنده , , Gerd Steiner، نويسنده ,
Abstract :
Novel 5-HT1 autoreceptor ligands based on the N-4-aryl-piperazinyl-N′-ethyl-5,6,7,8-tetrahydropyrido[4′, 3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one core are described. Aiming at antidepressants with a novel mode of action our objective was to identify potent antagonists showing balanced affinities and high selectivity for the 5-HT1A and 5-HT1B receptors. Strategies for the development of dual 5-HT1A and 5-HT1B antagonists based on 1 and 2 as leads and the corresponding results are discussed. Isoquinoline analogue 33 displayed high affinity and an antagonistic mode of action for the 5-HT1A and the 5-HT1B receptors and was characterized further with respect to selectivity, electrically stimulated [3H]5-HT release and in vivo efficacy.
