title: Autoradiographic localisation of D3-dopamine receptors in the human brain using the selective D3-dopamine receptor agonist (+)-[3H]PD 128907.
abstract: The selective D3-dopamine receptor agonist 4aR, 10bR-(+)-trans-3,4,4a, 10b-tetrahydro-4-[N-propyl-2,3-3H]-2H,5H-[1] benzopyrano[4,3-b]-1,4-oxazin-9-ol ([3H]PD 128907) was used to visualise D3-dopamine receptors in whole hemisphere cryosections from post-mortem human brain. [3H]PD 128907 has an 18- to 40-fold selectivity for D3- over D2-dopamine receptors as compared to a 7- to 24-fold selectivity of the more commonly used ligand [3H]7-OH-DPAT. [3H]PD 128907 accumulated markedly in the nucleus accumbens and in the ventral parts of caudate nucleus and putamen, with a slightly heterogeneous (patch-matrix like) distribution. The binding in the lateral parts of caudate nucleus and putamen was much less dense. No binding was obtained in any other regions. A very high proportion of [3H]PD 128907 was specifically bound, as judged from the low binding remaining in the presence of the D2/D3-dopamine receptor antagonist raclopride. This gives the ligand a potential for the detection of low density D3-dopamine receptors in the human brain. The binding obtained with [3H]PD 128907 was qualitatively similar to that using [3H]7-OH-DPAT in the presence of GTP. However, [3H]7-OH-DPAT labelled, in contrast to [3H]PD 128907, also D3-dopamine receptors in neocortex. The new compound [3H]PD 128907 appears to be a suitable radioligand for autoradiographic examination of the D3-dopamine receptor localisation in the human brain, and should also be useful for pharmacological studies of this receptor subtype.
authors.affiliation: Karolinska Institute, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Hall
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.forename: D
authors.initials: D
authors.lastname: Dijkstra
authors.forename: H
authors.initials: H
authors.lastname: Wikström
authors.forename: L D
authors.initials: LD
authors.lastname: Wise
authors.forename: T A
authors.initials: TA
authors.lastname: Pugsley
authors.forename: P
authors.initials: P
authors.lastname: Sokoloff
authors.forename: S
authors.initials: S
authors.lastname: Pauli
authors.forename: L
authors.initials: L
authors.lastname: Farde
authors.forename: G
authors.initials: G
authors.lastname: Sedvall
mesh_terms: D000328:Adult; D001345:Autoradiography; D001578:Benzopyrans / Q000032:analysis* / Q000037:antagonists & inhibitors; D001923:Brain Chemistry; D018491:Dopamine Agonists / Q000032:analysis*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000032:analysis* / Q000037:antagonists & inhibitors; D020891:Raclopride; D011954:Receptors, Dopamine / Q000032:analysis* / Q000187:drug effects; D012457:Salicylamides / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000032:analysis* / Q000037:antagonists & inhibitors
chemical_list: D001578:Benzopyrans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010078:Oxazines; D011954:Receptors, Dopamine; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D020891:Raclopride; D006160:Guanosine Triphosphate; C031349:7-hydroxy-2-N,N-dipropylaminotetralin