N-Alkylated 2-aminotetralins: central dopamine-receptor stimulating activity.
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 have been synthesized and evaluated. The compounds were tested biochemically and behaviorally for dopaminergic activity. From the biochemical data it is concluded that an n-propyl group on the nitrogen 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. It could be demonstrated that this is due to steric and not to lipophilic factors. It is suggested that a possible requirement for a potent agonist is that one of it 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 noradrenaline- or serotonin-receptor stimulating activity.
D006916:5-Hydroxytryptophan / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000138:chemical synthesis*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013997:Time Factors
D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D004295:Dihydroxyphenylalanine; D012110:Reserpine; D006916:5-Hydroxytryptophan