title: Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency.
abstract: Several novel cocaine analogs, previously shown to be very potent in in vitro binding studies, have been examined for their stimulatory effects on locomotor activity and for their ability to displace [3H]WIN 35,428 binding in vivo in mice. These compounds, like WIN 35,428, lack an ester link between the phenyl group and the tropane ring and have para-substitutions on the phenyl ring. They were much more potent than (-)-cocaine in producing increases in locomotor activity. In addition, they were more potent than (-)-cocaine in inhibiting [3H]WIN 35,428 binding in vivo in mouse striatum. Thus, these compounds demonstrate similar high potency in behavioral tests and in receptor binding assays, both in vivo and in vitro. Results support the hypothesis of a relationship between binding at the dopamine transporter and the behavioral effects of cocaine-like drugs. Further, assuming that maximal occupancy occurs with total displacement of [3H]WIN 35,428 binding in vivo, the data suggest that maximal locomotor effects occur with near total occupancy of transporter binding sites.
authors.affiliation: Neuroscience Branch, National Institute on Drug Abuse Addiction Research Center, Baltimore, Maryland.
authors.forename: E J
authors.initials: EJ
authors.lastname: Cline
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: J W
authors.initials: JW
authors.lastname: Boja
authors.forename: F I
authors.initials: FI
authors.lastname: Carroll
authors.forename: J L
authors.initials: JL
authors.lastname: Katz
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuhar
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine