Sigma receptors and cocaine abuse.
Sigma receptors have been well documented as a protein target for cocaine and have been shown to be involved in the toxic and stimulant actions of cocaine. Strategies to reduce the access of cocaine to sigma receptors have included antisense oligonucleotides to the sigma-1 receptor protein as well as small molecule ligand with affinity for sigma receptor sites. These results have been encouraging as novel protein targets that can attenuate the actions of cocaine are desperately needed as there are currently no medications approved for treatment of cocaine toxicity or addiction. Many years of research in this area have yet to produce an effective treatment and much focus was on dopamine systems. A flurry of research has been carried out to elucidate the role of sigma receptors in the blockade of cocaine effects but this research has yet to yield a clinical agent. This review summarizes the work to date on the linkage of sigma receptors and the actions of cocaine and the progress that has been made with regard to small molecules. Although there is still a lack of an agent in clinical trials with a sigma receptor mechanism of action, work is progressing and the ligands are becoming more selective for sigma systems and the potential remains high.
Department of Medicinal Chemistry, School of Pharmacy, The University of Mississippi, University, 38677, USA.
Sanju
S
Narayanan
Christophe
C
Mesangeau
Jacques H
JH
Poupaert
Christopher R
CR
McCurdy
D000818:Animals; D003042:Cocaine / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000097605:Sigma-1 Receptor
D003042:Cocaine; D004298:Dopamine; D018492:Dopamine Antagonists; D008024:Ligands; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D011619:Psychotropic Drugs; D011954:Receptors, Dopamine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor