title: Pharmacological profile of a chromanamine analogue (DP-6OH-3CA) of the selective presynaptic dopamine agonist N,N-dipropyl-7-hydroxy-2-aminotetralin.
abstract: The pharmacological profile of an oxygen isostere of the selective presynaptic dopamine agonist DP-7OH-AT, i.e. dipropyl-6-hydroxy-3-chromanamine (DP-6OH-3CA) has been evaluated in various receptor binding, neurobiochemical and behavioural experiments. The chromanamine displaced the 3H-labelled dopamine ligands, 5,6-DPAT and N-0437, with Ki values of 106 and 143 nM, respectively. In in-vivo biochemical models for presynaptic activity the chromanamine induced a half-maximal effect in the gamma-butyrolactone reversal test at 6.8 mumol kg-1 and had an ED70 value of 40 mumol kg-1 for HVA decrease in the striatum. In behavioural models for postsynaptic dopaminergic activity a half-maximal effect for the induction of stereotypy was reached at 100 mumol kg-1 and reversal of the effects of reserpine to a level of 200 counts was induced at 11 mumol kg-1. On comparison of these results with the results obtained with the carbon analogue of DP-6OH-3CA, i.e. DP-7OH-AT, it is apparent that the chromanamine has a reduced potency for dopamine D2 receptors in in-vitro and in-vivo models. The selectivity for presynaptic dopamine receptors was lower than with DP-7OH-AT and the isomeric chromanamine, DP-8OH-3CA, indicating that the optimal position of the hydroxyl group for presynaptic selectivity is in the 8 and not in the 6 position for the chromanamines.
authors.affiliation: Department of Medicinal Chemistry, Subfaculty of Pharmacy, University of Groningen, The Netherlands.
authors.forename: N A
authors.initials: NA
authors.lastname: Vermue
authors.forename: D
authors.initials: D
authors.lastname: Dijkstra
authors.forename: A S
authors.initials: AS
authors.lastname: Horn
mesh_terms: D015107:4-Butyrolactone / Q000037:antagonists & inhibitors; D000818:Animals; D001578:Benzopyrans / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002417:Cattle; D003342:Corpus Striatum / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D012110:Reserpine / Q000037:antagonists & inhibitors; D013239:Stereotyped Behavior / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D015259:Dopamine Agents; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C055143:6-hydroxy-3,4-dihydro-3-(dipropylamino)-2H-1-benzopyran; D004295:Dihydroxyphenylalanine; D012110:Reserpine; D015107:4-Butyrolactone; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine