1-Aryl-1,4-dihydro-3(2H)-isoquinolinones: Two modes of interaction with 5-HT1A receptors

Two series of 1-aryl-1,4-dihydro-3(2H)-isoquinoline derivatives were synthe sized, and their in vitro and in vivo properties at 5-HT1A and 5-HT2A recep tors were evaluated. In was shown that series a, containing a 1-(m-chlophen yl)piperazine fragment, interacts with 5-HT1A receptors in two different mo des: as an ordinary 4-substituted 1-arylpiperazine and as a pseudo one. Ser ies b, with a 1,2,3,4-tetrahydroisoquinoline moiety, binds to the receptor thanks to a pseudo 1-arylpiperazine fragment. Regardless of the mode of int eraction, both those series demonstrated 5-HT1A receptor antagonistic prope rties in animal models. Different in vivo properties of 2b, due to a 7-meth oxy substituent, indicate that the isoquinolinone portion also interacts wi th 5-HT1A receptors.