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

(+)-2-[ I-123]A-69024, [(+)-1-(2-[I-123]iodo-4,5-dimethoxy-benzyl)-7-hydrox y-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline]. is a specific acid en antioselective dopamine D1 receptor radioligand. The in vivo biodistributio n of this radioligand in rats showed high brain uptake and a distribution c onsistent with the density of dopamine D1 receptors. Highest uptake was obs erved in the striatum (0.65 %ID/g) at 5 min followed by clearance, As a mea sure 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 clozapin e (D4) displayed no inhibitory effect on (+)2-[I-123]A-69024 accumulation i n any brain region. Ketanserin (5-HT2/5-HT2C) and haloperidol (D2 receptor antagonist/sigma receptor ligand) also displayed no inhibitory effect in an y brain region studied. With the pharmacologically inactive enantiomer, (-) -2-[I-123]A-69024. the brain uptake was determined to be non-specific since a striatum/cerebellar ratio of near 1 was observed throughout the time cou rse of the experiment. (+)-2-[I-123]A-69024 displays enantioselectivity for dopamine D1 receptors and may deserve further investigation as a possible SPECT radioligand, (C) 2001 Elsevier Science Inc. All rights reserved.