Selective behavioral alterations on addition of a 4'-phenyl group to cocaine.
We synthesized a cocaine analog in which a phenyl group was added at the para-position of the benzene ring of cocaine. This substitution caused a modest reduction (four-fold compared with cocaine) in binding potency for the primate (Papio) dopamine transporter as judged by displacement of [3H]WIN 35,428 binding from caudate/putamen membranes. Behavioral effects of this structural modification in the mouse were complex and selective, comprising absence of stimulation of locomotor activity, enhanced inhibition of locomotion and reduced lethal potency. Convulsant potency was unaltered. Substituents at the 4'-position of cocaine are important in its actions. Simple changes in the chemical structure of this drug may produce complex and selective changes in its neurochemical and behavioral actions.
Seale
T W
TW
Department of Pediatrics, University of Okalhoma Health Sciences Center, Oklahoma City 73190, USA.
Niekrasz
I
I
Chang
F
F
Singh
S
S
Basmadjian
G P
GP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000138:chemical synthesis / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000138:chemical synthesis / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D010215:Papio; D011485:Protein Binding / Q000187:drug effects
C101674:4'-phenylcocaine; D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D003292:Convulsants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009294:Narcotics; D009419:Nerve Tissue Proteins; D003042:Cocaine