Evidence for dopamine 'D1-like' receptor subtypes in the behavioural effects of two new selective antagonists, LY 270411 and BW 737C.
A new, chemically distinct antagonist at dopamine 'D1-like' receptors, the thienoazepine LY 270411, ([+]-2(3-chloro-6-methyl-8-phenyl-5,6,7,8 -tetrahydro-4H-thieno[2,3d]azepin-2-yl)propan-2-ol) was compared with the isoquinoline BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4- propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) and the benzazepine SCH 23390 ([R]-7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1 H-3-benzazepine) for effects on behavioural responses to the isochroman full efficacy dopamine 'D1-like' receptor agonist A 68930 ([1R,3S]-1-aminomethyl-5, 6-dihydroxy-3-phenylisochroman) vs. the dopamine 'D2-like' receptor agonist RU 24213 (N-n-propyl-N-phenylethyl-p-3-hydroxyphenylethylamine). Grooming responses to A 68930 were readily blocked by each of LY 270411, BW 737C and SCH 23390; however, the vacuous chewing response was blocked only by BW 737C. Sniffing and locomotor responses to RU 24213 were attenuated by BW 737C and SCH 23390 but not by LY 270411; furthermore, myoclonic jerking to RU 24213 was released by BW 737C and SCH 23390 but not by LY 270411. These findings indicate that grooming induced by dopamine 'D1-like' receptor agonism is blocked by all chemical classes of dopamine 'D1-like' receptor antagonist while vacuous chewing is blocked only by isoquinoline dopamine 'D1-like' receptor antagonism; this suggests that these behaviours may be mediated via functionally and pharmacologically distinct subtypes of dopamine 'D1-like' receptor. Furthermore, LY 270411 appears unique in its activity to readily block 'D1-like' receptor agonist-induced grooming without influencing behavioural responses to dopamine 'D2-like' receptor agonism; thus, the site mediating prototypical dopamine 'D1-like' receptor agonist-induced behaviours may be dissociable pharmacologically from dopamine 'D1-like' site(s) participating in functional interactions with dopamine 'D2-like' receptors.
Deveney
A M
AM
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
Waddington
J L
JL
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006120:Grooming / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D044005:Tetrahydroisoquinolines
D001381:Azepines; D002839:Chromans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007546:Isoquinolines; C104914:LY 270411; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D044005:Tetrahydroisoquinolines; C075318:BW 737C89; D013134:Spiperone; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; C065380:A 68930