1. J Med Chem. 2008 Mar 13;51(5):1482-6. Epub 2008 Feb 16.

Conversion of a highly selective sigma-1 receptor-ligand to sigma-2 receptor
preferring ligands with anticocaine activity.

Mésangeau C, Narayanan S, Green AM, Shaikh J, Kaushal N, Viard E, Xu YT, Fishback
JA, Poupaert JH, Matsumoto RR, McCurdy CR.

Department of Medicinal Chemistry, The University of Mississippi, Mississippi
38677, USA.

Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1
receptors. The involvement of sigma-2 receptors remains unclear. To investigate
their potential role, we have designed compounds through a convergent synthesis
utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2
ligand. Among the synthesized compounds was produced a subnanomolar sigma-2
ligand with an 11-fold preference over sigma-1 receptors. These compounds may be 
useful in developing effective pharmacotherapies for cocaine toxicity.

PMID: 18278854 [PubMed - indexed for MEDLINE]