Novel dopamine receptor agonists and antagonists with preferential action on autoreceptors.
The enantiomers of cis-5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin and its methyl ether have been synthesized. The compounds were tested for central dopamine (DA) receptor activity, by using biochemical and behavioral tests in rats. The (1R,2S)-(-) enantiomers of 1 and 2 are characterized as centrally acting DA-receptor agonists while the corresponding (1S,2R)-(+) enantiomers are characterized as centrally acting DA-receptor antagonists. Compounds (+)-1 and (+)-2 differ from classical neuroleptics in being able to increase DA synthesis rate in a wide dose range without reducing locomotor activity, suggesting a pronounced selectivity for DA autoreceptors. Also the (-) enantiomers seem to act preferentially on DA autoreceptors.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000494:pharmacology*
D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C045971:UH 232; C045972:5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin