Facile syntheses of potent dopaminergic argonists and their effect on neurotransmitter release.
The facile syntheses of important intermediates used in the preparation of the two potent dopaminergic argonists, 2-amino-6,7-dihydroxytetrahydronaphthalene (11) (referred to by some authors as ADTN) and its 5,6-dihydroxyl isomer 12, are described. Thus 6,7-dimethyoxy-2-tetralone has been prepared in two steps and 5,6-dimethoxy-2-tetralone in three steps both from commercially available materials. The effects of 11, 12, and the noncatechol analogue, 2-aminotetrahydronaphthalene (ATN), on radioactive neurotransmitter release have been studied in vitro using rat brain slices. It has been shown that both 11 and 12, at a concentraiton of 2 micron, cause a release of [3H]-DA and NA, 11 being more potent than 12 in releasing [3H]-DA. ATN (2 micron) was found to be inactive in these experiments which shows the importance of the catechol function in this uptake--release process.
D000322:Adrenergic Agonists / Q000138:chemical synthesis*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009281:Naphthalenes / Q000138:chemical synthesis*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014316:Tritium
D000322:Adrenergic Agonists; D009281:Naphthalenes; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D014316:Tritium; D004298:Dopamine; D009638:Norepinephrine