N-arylalkylpiperidines as high-affinity sigma-1 and sigma-2 receptor ligands: phenylpropylamines as potential leads for selective sigma-2 agents.
To delineate the differences between the structural requirements necessary for recognition at sigma-1 and sigma-2 receptors, a range of phenethyl- and phenylpropylpiperidines were evaluated in binding assays. Phenethylpiperidines were found to favor sigma-1 receptors, whereas phenylpropylpiperidines tend to favor sigma-2 receptors. It appears that phenylpropylamine is a potential pharmacophore for selective sigma-2 ligands.
Maeda
Dean Y
DY
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD 21201, USA.
Williams
Wanda
W
Kim
Wes E
WE
Thatcher
Linn N
LN
Bowen
Wayne D
WD
Coop
Andrew
A
D014150:Antipsychotic Agents / Q000138:chemical synthesis; D001667:Binding, Competitive / Q000187:drug effects; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011437:Propylamines / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D017480:Receptors, sigma / Q000187:drug effects*; D013329:Structure-Activity Relationship; D000097605:Sigma-1 Receptor
D014150:Antipsychotic Agents; D008024:Ligands; D010880:Piperidines; D011437:Propylamines; D011725:Pyridines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor