title: Pharmacological evaluation of (+)-2- [123I]A-69024: a radioligand for in vivo studies of dopamine D1 receptors.
abstract: (+)-2-[123I] A-69024, [(+)-1-(2-[123I] iodo-4,5-dimethoxy-benzyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline], is a specific and enantioselective dopamine D1 receptor radioligand. The in vivo biodistribution of this radioligand in rats showed high brain uptake and a distribution consistent with the density of dopamine D1 receptors. Highest uptake was observed in the striatum (0.65 %ID/g) at 5 min followed by clearance. As a measure of specificity the striatum/cerebellar ratio reached a maximum of 3.9 at 30 min post-injection. Radioactivity in the striatum was reduced by 68% by pre-administration of the D1 antagonist SCH 23390. Pre-administration of other dopamine binding drugs, spiperone (D2), 7-OH-DPAT (D3), and clozapine (D4) displayed no inhibitory effect on (+)-2-[123I]A-69024 accumulation in any brain region. Ketanserin (5-HT2/5-HT2C) and haloperidol (D2 receptor antagonist/sigma receptor ligand) also displayed no inhibitory effect in any brain region studied. With the pharmacologically inactive enantiomer, (-)-2-[123I]A-69024, the brain uptake was determined to be non-specific since a striatum/cerebellar ratio of near 1 was observed throughout the time course of the experiment. (+)-2-[123I]A-69024 displays enantioselectivity for dopamine D1 receptors and may deserve further investigation as a possible SPECT radioligand.
authors.affiliation: Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. mkassiou@nucmed.rpa.cs.nsw.gov.au
authors.forename: M
authors.initials: M
authors.lastname: Kassiou
authors.forename: K
authors.initials: K
authors.lastname: Mardon
authors.forename: F
authors.initials: F
authors.lastname: Mattner
authors.forename: A
authors.initials: A
authors.lastname: Katsifis
authors.forename: B
authors.initials: B
authors.lastname: Dikic
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006220:Haloperidol / Q000494:pharmacology; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D007650:Ketanserin / Q000494:pharmacology; D008024:Ligands; D008297:Male; D010208:Papaverine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D013134:Spiperone / Q000494:pharmacology; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D008024:Ligands; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; D013764:Tetrahydronaphthalenes; D013134:Spiperone; C061450:A 69024; D007650:Ketanserin; D010208:Papaverine; D003024:Clozapine; D006220:Haloperidol; C031349:7-hydroxy-2-N,N-dipropylaminotetralin