N-Alkylated 2-aminotetralins: central dopamine-receptor stimulating activity

Abstract

In order to define the structural requirements of N-substituents of 2-aminotetralins as central dopamine receptor agonists, a series of N-alkyl- and N,N-dialkyl-substituted 2-amino-5-hydroxy- and 2-amino-5-methoxytetralins were synthesized and evaluated. The compounds were tested biochemically and behaviorally in rats for dopaminergic activity. An n-propyl group on the N is optimal for activity. The corresponding N-ethyl-substituted compounds are slightly less active, while the absence of N-ethyl or N-propyl groups give almost inactive compounds. This is due to steric and not to lipophilic factors. Apparently a possible requirement for a potent agonist is that one of its N substituents must fit into a receptor cavity which, because of its size, can maximally accommodate an n-propyl but also smaller groups like ethyl or methyl. The active compounds appeared to give a similar relative pre- and postsynaptic stimulation and had also similar activities for the limbic system and for striatum. None of the compounds listed seemed to have central norepinephrine or serotonin-receptor stimulating activity.