New, potent cocaine analogs: ligand binding and transport studies in rat striatum.
Two potent cocaine analogs have been developed that have the highest known affinities for the cocaine binding site in rat striatum. Both 3 beta-(4-chlorophenyl)- (RTI-COC-31) and 3 beta-(4-methylphenyl)-tropane-2-carboxylic acid methyl ester (RTI-COC-32) compete for [3H]WIN 35,428 and [3H]mazindol binding with a IC50 that is 100 times more potent than that of (-) cocaine. Additionally, these compounds inhibit [3H]dopamine uptake with a similar, high potency. These results may lead to the development of high affinity probes for the cocaine binding site.
Boja
J W
JW
Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Carroll
F I
FI
Rahman
M A
MA
Philip
A
A
Lewin
A H
AH
Kuhar
M J
MJ
D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D011869:Radioligand Assay; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
C067731:3-(4-chlorophenyl)tropane-2-carboxylic acid methyl ester; C067730:RTI-COC 32; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; C021278:troparil; D003042:Cocaine; D004298:Dopamine