Volk B.,Chemical Research Division |
Gacsalyi I.,Preclinical Research Division |
Pallagi K.,Preclinical Research Division |
Poszavacz L.,Chemical Research Division |
And 6 more authors.
Journal of Medicinal Chemistry | Year: 2011
A series of (arylpiperazinylbutyl)oxindoles as highly potent 5-HT 7 receptor antagonists has been studied for their selectivity toward the 5-HT 1A receptor and α 1-adrenoceptor. Several derivatives exhibited high 5-HT 7/5-HT 1A selectivity, and the key structural factors for reducing undesired α 1-adrenergic receptor binding have also been identified. Rapid metabolism, a common problem within this family of compounds, could be circumvented with appropriate substitution patterns on the oxindole carbocycle. Contrary to expectations, none of the compounds produced an antidepressant-like action in the forced swimming test in mice despite sufficiently high brain concentrations. On the other hand, certain analogues showed significant anxiolytic activity in two different animal models: the Vogel conflict drinking test in rats and the light-dark test in mice. © 2011 American Chemical Society.