New putative selective agonists at the D-1 dopamine receptor: behavioural and neurochemical comparison of CY 208-243 with SK&F 101384 and SK&F 103243.
Three putative D-1 agonists with nonbenzazepine structures were compared with the prototype benzazepine D-1 partial agonist SK&F 38393 for their behavioural effects in the intact adult rat, and for their relative affinities for D-1 and D-2 dopamine receptors in vitro. SK&F 103243, a restricted conformation analogue of SK&F 38393, and SK&F 101384 (8-Cl-ADTN) showed low affinity for D-1 and D-2 receptors in in vitro binding studies, and failed to induce any behavioural effects on peripheral administration. CY 208-243, an indolophenanthridine derivative, showed appreciable affinity not only for D-1 receptors but also for D-2 receptors, while in behavioural studies it showed some of the characteristics of a partial D-1 dopamine receptor agonist; thus, it failed to promote stereotyped behaviour, but induced episodes of intense grooming which were sensitive to blockade by the D-1 antagonist SCH 23390. No such effect was induced by the selective D-2 agonist RU 24213. CY 208-243 is the first nonbenzazepine which shows some of the properties of a D-1 agonist in the intact adult animal. However, the differences between its in vitro binding characteristics and its functional properties remain enigmatic.
Murray
A M
AM
Department of Clinical Pharmacology, Royal College of Surgeons, Dublin, Ireland.
Waddington
J L
JL
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D015259:Dopamine Agents; D005449:Fluorenes / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D010617:Phenanthridines / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1; D013239:Stereotyped Behavior / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001552:Benzazepines; D015259:Dopamine Agents; D005449:Fluorenes; D007211:Indoles; D009281:Naphthalenes; D010617:Phenanthridines; D010627:Phenethylamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D013764:Tetrahydronaphthalenes; C054531:CY 208-243; C063397:SK&F 101384; C050330:SK&F 103243; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride