8-Hydroxy-2-(alkylamino)tetralins and related compounds as central 5-hydroxytryptamine receptor agonists.
A series of 2-(alkylamino)tetralins related to 8-hydroxy-2-(di-n-propylamino)tetralin (21) were prepared and tested as dopamine (DA) and 5-hydroxytryptamine (5-HT) receptor agonists. Several of the compounds were potent 5-HT agonists devoid of DA-mimetic effects. N-Ethyl or N-propyl substitution of 8-hydroxy-2-aminotetralin gave the most potent agonists. It was shown that the most potent compound, (+)-21, has the 2R configuration. 5,8-Di-methoxy-2-(di-n-propylamino)tetralin (31) was found to be a weak DA agonist devoid of 5-HT activity. The corresponding indan derivative, 4,7-dimethoxy-2-(di-n-propylamino)indan (39), has been reported to be active on both DA and 5-HT receptors. The 5-HT-stimulating properties of compounds 21 and 39 as compared to the incapability of compound 31 to activate the 5-HT receptor is tentatively explained by the assumed mode of binding of the compounds to the 5-HT receptor.
D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D007202:Indicators and Reagents; D008297:Male; D009281:Naphthalenes / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology
D007202:Indicators and Reagents; D009281:Naphthalenes; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D012110:Reserpine