title: Synthesis and dopaminergic activity of pyridine analogs of 5-hydroxy-2-(di-n-propylamino)tetralin.
abstract: The pyridine analogs of 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT), 4-6, were synthesized, and their biological activity was compared to that of 5-OH-DPAT. Compounds 4 and 6 exhibited activity similar to 5-OH-DPAT in dopamine (DA) D2 and D3 receptor binding and in autoreceptor activation as measured by their ability to reverse the gamma-butyrolactone-induced increase in rat DA synthesis. Behaviorally, 4 and 6 decreased locomotor activity (LMA) in rats (sc) at low doses but did not increase LMA to the same extent as 5-OH-DPAT at higher doses, indicating that 4 and 6 may be more selective for the DA autoreceptor. While 4 was less active orally in rats, 6 appeared to retain most of its behavioral potency. Analog 5 showed little activity in vivo or in vitro.
authors.affiliation: Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Glase
authors.forename: A E
authors.initials: AE
authors.lastname: Corbin
authors.forename: T A
authors.initials: TA
authors.lastname: Pugsley
authors.forename: T G
authors.initials: TG
authors.lastname: Heffner
authors.forename: L D
authors.initials: LD
authors.lastname: Wise
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015259:Dopamine Agents / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D015259:Dopamine Agents; D011725:Pyridines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C011799:5-hydroxy-2-N,N-dipropylaminotetralin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin