Trifluoromethoxyl substituted phenylethylene diamines as high affinity sigma receptor ligands with potent anti-cocaine actions.
The phenylethylene diamines are a class of sigma receptor ligands with excellent selectivity over other biological systems and with anti-cocaine actions that involve antagonism of sigma1 receptors. In order to increase the potency of the aromatic methoxyl substituted analogues, trifluoromethoxyl groups were introduced to prevent metabolic demethylation. The para-substituted trifluoromethoxyl substituted analogues were shown to have increased sigma receptor affinity and represent the most potent anti-cocaine phenylethylene diamines yet described.
Smith
Trudy A
TA
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Yang
Xiaowen
X
Wu
Huifang
H
Pouw
Buddy
B
Matsumoto
Rae R
RR
Coop
Andrew
A
D000818:Animals; D001921:Brain / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D010627:Phenethylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship
D003959:Diamines; D008024:Ligands; D010627:Phenethylamines; D017480:Receptors, sigma