title: Pharmacological profiles of three new, potent and selective dopamine receptor agonists: N-0434, N-0437 and N-0734.
abstract: A series of new dopamine (DA) receptor agonists, of the 2-aminotetralin group, i.e. N-0434, N-0437 and N-0734 were investigated in both in vivo and in vitro pharmacological test systems. In vivo, the reversal of the gamma-butyrolactone-induced increase in rat central DOPA biosynthesis rate was taken as a measure of presynaptic activity. In addition, the homovanillic acid (HVA) decrease, after intraperitoneal and after oral administration of the drugs was also taken as a measure of presynaptic activity. Postsynaptic activity was measured in two behavioural models, i.e. reserpine reversal and stereotypy induction. The effects of these drugs on noradrenaline and dopamine turnover (alpha-MpT method) were studied in addition. The displacement of [3H]N,N-dipropyl-5,6-dihydroxy-2-aminotetralin [( 3H]DP-5,6-ADTN) binding to rat striatal homogenates was studied in vitro. The results indicate that all three compounds are potent and selective DA agonists that lack significant alpha 2 activity. Because of its long duration of action and high oral activity, N-0437 seems to be a most promising candidate for further evaluation for possible therapeutic use.
mesh_terms: D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000037:antagonists & inhibitors; D013239:Stereotyped Behavior / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors; D019805:alpha-Methyltyrosine
chemical_list: D008781:Methyltyrosines; D009281:Naphthalenes; D010627:Phenethylamines; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C049856:N 0734; D019805:alpha-Methyltyrosine; C041369:2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin; C047508:rotigotine; D012110:Reserpine; D015107:4-Butyrolactone; D004298:Dopamine; D009638:Norepinephrine