Pharmacological evaluation of (+)-2-[123I]A-69024 A radioligand for in vivo studies of dopamine D1 receptors

Kassiou, Michael, Mardon, Karine, Mattner, Filomena, Katsifis, Andrew and Dikic, Branko (2001) Pharmacological evaluation of (+)-2-[123I]A-69024 A radioligand for in vivo studies of dopamine D1 receptors. Life Sciences, 69 6: 669-675. doi:10.1016/S0024-3205(01)01156-0


Author Kassiou, Michael
Mardon, Karine
Mattner, Filomena
Katsifis, Andrew
Dikic, Branko
Title Pharmacological evaluation of (+)-2-[123I]A-69024 A radioligand for in vivo studies of dopamine D1 receptors
Formatted title
Pharmacological evaluation of (+)-2-[123I]A-69024 A radioligand for in vivo studies of dopamine D1 receptors
Journal name Life Sciences   Check publisher's open access policy
ISSN 0024-3205
Publication date 2001-06-29
Sub-type Article (original research)
DOI 10.1016/S0024-3205(01)01156-0
Volume 69
Issue 6
Start page 669
End page 675
Total pages 7
Place of publication New York, USA
Publisher Elsevier Science
Language eng
Subject 111502 Clinical Pharmacology and Therapeutics
110502 Dental Therapeutics, Pharmacology and Toxicology
Formatted 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/σ 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.
Keyword (+)-2-[123I]A-69024
Enantioselectivity
Dopamine D1 receptors
SPECT
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Thu, 22 Jul 2010, 01:10:45 EST by Laura McTaggart on behalf of School of Medicine