Actions of (+/-)-7-hydroxy-N,N-dipropylaminotetralin (7-OH-DPAT) on dopamine synthesis in limbic and extrapyramidal regions of rat brain.
The proposed D3-selective ligand (+/-)-7-hydroxy-N,N-dipropylaminotetralin (7-OH-DPAT) inhibited tyrosine hydroxylase in vitro (IC50 = 0.6-0.7 microM) and dihydroxyphenylalanine (DOPA) accumulation in vivo (ID50 = 4.8-6.4 mg/kg) in two autoreceptor models in extrapyramidal and limbic tissue in rat forebrain, without consistent regional selectivity. Some limbic selectivity (ID50 = 10 vs. 29 mg/kg) was found in an in vivo model permitting expression of postsynaptic D3 and D2 receptor activity. The effects were partially blocked by S(-)-eticlopride alone, and fully after reserpine pretreatment. The results suggest that 7-OH-DPAT activates D3 or D2 autoreceptors, alters dopamine storage or release, and may interact with some limbic selectivity at postsynaptic D3 and D2 receptors as a partial agonist.
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
R G
RG
Booth
R J
RJ
Baldessarini
E
E
Marsh
C E
CE
Owens
D000818:Animals; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D018491:Dopamine Agonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005116:Extrapyramidal Tracts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008032:Limbic System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3; D012110:Reserpine / Q000494:pharmacology; D012457:Salicylamides / Q000494:pharmacology; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D004295:Dihydroxyphenylalanine; D012110:Reserpine; D014446:Tyrosine 3-Monooxygenase; C045989:eticlopride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine