(+/-)-7-chloro-8-hydroxy-1-(4'-[125I]iodophenyl)-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine: a potential CNS D-1 dopamine receptor imaging agent.
Synthesis, radiolabeling, and in vitro and in vivo properties of an iodinated benzazepine, (+/-)-7-chloro-8-hydroxy-1-(4'-[125I]iodophenyl)-3- methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, [125I]FISCH, as a potential imaging agent for evaluation of central nervous system (CNS) D-1 dopamine receptors in humans, were investigated. After an iv injection, this benzazepine derivative showed good brain uptake in rats (2.27, 1.40, 0.55% dose/whole brain at 2, 15, and 60 min, respectively). The striatum/cerebellum ratio was high (2.47 at 60 min after the injection). The binding affinity of this agent in rat striatum tissue preparation displayed a Kd of 1.43 +/- 0.15 nM. Competition data (in vitro) showed the following rank order of potency: SCH-23390 greater than (+/-)-FISCH greater than (+/-)-IBZP much greater than apomorphine greater than WB 4010 greater than ketanserin approximately spiperone. The preliminary data suggest that the agent is highly selective for the CNS D-1 receptor.
Chumpradit
S
S
Department of Radiology, University of Pennsylvania, Philadelphia 19104.
Kung
H F
HF
Billings
J
J
Kung
M P
MP
Pan
S
S
D000818:Animals; D001552:Benzazepines; D001921:Brain / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007463:Iodobenzoates; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1; D014018:Tissue Distribution
D001552:Benzazepines; D007463:Iodobenzoates; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C060141:7-chloro-8-hydroxy-1-(4'-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine