title: Dopamine receptor agonist potencies for inhibition of cell firing correlate with dopamine D3 receptor binding affinities.
abstract: The potencies for in vivo inhibition of substantia nigra pars compacta dopamine single cell firing were determined for apomorphine, BHT 920, N-0923, (+/-)-7-hydroxy-dipropylaminotetralin (7-OH-DPAT), (+)-3-(3-hydroxyphenyl)-N-propylpiperidine (3-PPP), pramipexole, quinelorane, quinpirole, RU 24926, U-86170, and U-91356. Significant correlation was obtained between the potencies of these 11 highly efficacious dopamine receptor agonists and the in vitro binding affinities at dopamine D3 receptors, but not at dopamine D2L receptors. These results support a functional role for the dopamine D3 receptor subtype in the autoreceptor-mediated regulation of dopamine cell activity, while a role for dopamine D2 receptors awaits further analysis. In addition, the results demonstrate the limitations of using currently available dopamine receptor agonists to delineate relative in vivo roles for the dopamine D2 and D3 receptor subtypes.
mesh_terms: D000634:Aminoquinolines / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000378:metabolism / Q000494:pharmacology; D001381:Azepines / Q000378:metabolism / Q000494:pharmacology; D052160:Benzothiazoles; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000378:metabolism / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D000077487:Pramipexole; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3; D013329:Structure-Activity Relationship; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000494:pharmacology; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
chemical_list: D000634:Aminoquinolines; D001381:Azepines; D052160:Benzothiazoles; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D004873:Ergolines; D007093:Imidazoles; D010627:Phenethylamines; D010880:Piperidines; D011804:Quinolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D013844:Thiazoles; D013876:Thiophenes; C073698:5-(dipropylamino)-5,6-dihydro-4H-imidazo-(5,1ij)quinolin-2(1H)-one; C083374:5-propylamino-5,6-dihydro-4H-imidazo(4,5,1-ij)quinolin-2(1H)-one; D019257:Quinpirole; C025254:RU 24926; C024763:talipexole; D000077487:Pramipexole; C047508:rotigotine; C026539:preclamol; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; C047726:quinelorane