Add time:07/17/2019 Source:sciencedirect.com
SummaryIn order to further explore the structure—activity relationships of serotonergic 2-aminotetralin derivatives, a total of 12 aryl and heteroaryl substituents have been introduced in the C8-position of 2-(dipropylamino)tetralin. The affinity of the compounds was studied by competition experiments with [3H]-8-OH-DPAT in rat-brain tissue. In addition, the effects of the compounds were assessed in vivo using biochemical and behavioral tests in rats. Although all the novel derivatives had fairly high affinities for the 5-HT1A receptors, several compounds failed to produce biochemical or behavioral effects indicative of 5-HT1A receptor stimulation. In addition, they did not appear to be 5-HT1A-receptor antagonists. Hence, the apparent inactivity in vivo may be due to pharmacokinetic factors such as extensive metabolism or poor ability to pass the blood—brain barrier. However, a few compounds in the present series, such as (S)-8-(2-furyl)-2-(dipropylamino)tetralin, did produce most of the in vivo pharmacological actions typical of 5-HT1A receptor agonists.
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