title: In vivo characterization of novel full and partial 2-(4-aminophenyl)-N,N-dipropylethylamine dopamine D(2) receptor agonists.
abstract: Behavioral and biochemical techniques were used to compare the in vivo intrinsic efficacy of two new 2-(4-aminophenyl)-N, N-dipropylethylamine dopamine D(2) receptor agonists, 2-(4-amino-3-trifluoromethylphenyl)-N-N-dipropyl-ethylamine (NBF-203) and 2-(4-amino-3-bromo-5-trifluoromethylphenyl)-N-N-dipropylethylamine (NBF-234). Adult male Sprague-Dawley rats were used as experimental animals. NBF-203 was characterized as a full dopamine D(2) receptor agonist, whereas NBF-234 displayed properties of a partial agonist, or antagonist, at dopamine D(2) receptors. Thus, NBF-203 produced effects similar to those of apomorphine in models for dopamine synthesis, release and turnover. As a strong indication of markedly less intrinsic efficacy, the administration of NBF-234 did not result in antagonism of reserpine-induced suppression of locomotor activity in the presence of (+/-)-1-phenyl-2,3,4,5, -tetrahydro-(1H)-3-benzazepine-7,8-diol HCl (SKF-38393)-induced dopamine D(1) receptor activation. The present series of compounds offer the possibility of adjusting intrinsic efficacy at dopamine D(2) receptors, and such fine-tuning could be an important strategy in the search for optimal antipsychotic or antiparkinson drugs within the partial dopamine D(2) receptor agonist concept.
authors.affiliation: Department of Pharmacology, Astra Arcus, SE-151 85, Södertälje, Sweden. sven.ahlenius@fyfa.ki.se
authors.forename: S
authors.initials: S
authors.lastname: Ahlenius
authors.forename: E
authors.initials: E
authors.lastname: Ericson
authors.forename: L
authors.initials: L
authors.lastname: Florvall
authors.forename: P
authors.initials: P
authors.lastname: Jiménez
authors.forename: V
authors.initials: V
authors.lastname: Hillegaart
authors.forename: A
authors.initials: A
authors.lastname: Wijkström
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000096:biosynthesis; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D005021:Ethylamines / Q000494:pharmacology*; D005464:Fluorobenzenes / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012110:Reserpine / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D018491:Dopamine Agonists; D005021:Ethylamines; D005464:Fluorobenzenes; D018757:GABA Modulators; D008996:Monoamine Oxidase Inhibitors; C410292:NBF 203; C410293:NBF 234; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D004295:Dihydroxyphenylalanine; D019805:alpha-Methyltyrosine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D012110:Reserpine; D010293:Pargyline; D015107:4-Butyrolactone; D004298:Dopamine