title: Non-competitive inhibitory activities of morphinan and morphine derivatives at the alpha 3 beta 4 Neuronal nicotinic acetylcholine receptor determined using nonlinear chromatography and chemometric techniques.
abstract: OBJECTIVE
  A series of morphine and morphinan derivatives were chromatographed on a column containing immobilized cellular membranes from a cell line expressing the alpha 3 beta 4 neuronal nicotinic acetylcholine receptor (alpha 3 beta 4 nAChR).
  
  
  METHODS
  The results were analyzed using chemometric and molecular modeling techniques in order to predict the noncompetitive inhibitory (NCI) activity of these compounds, the molecular basis for the predicted activity and the binding sites of the inhibitors.
  
  
  RESULTS
  The data demonstrated that seven of seven morphinans were NCIs and bound in the central lumen of the nAChR while only 2 of 13 morphine derivatives had NCI activity and these compounds most likely bound at the quinacrine binding site on the nAChR. The predicted activities were confirmed using functional inhibition studies.
  
  
  CONCLUSIONS
  The results indicate that this approach can be used to rapidly assess pharmacological activity and to guide new drug design.
authors.affiliation: Gerontology Research Center, National Institute on Aging/NIH, Baltimore, Maryland 21224-6825, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jozwiak
authors.forename: Ruin
authors.initials: R
authors.lastname: Moaddel
authors.forename: Rika
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Alexandre
authors.initials: A
authors.lastname: Maciuk
authors.forename: Irving W
authors.initials: IW
authors.lastname: Wainer
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D002846:Chromatography, Affinity; D006801:Humans; D008958:Models, Molecular; D009019:Morphinans / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D017711:Nonlinear Dynamics; D011796:Quinacrine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012414:Rubidium Radioisotopes; D013499:Surface Properties
chemical_list: D009019:Morphinans; D009022:Morphine Derivatives; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D012414:Rubidium Radioisotopes; C403530:nicotinic receptor alpha3beta4; D009538:Nicotine; D011796:Quinacrine