Quantitative conformational analyses predict distinct receptor sites for PCP-like and sigma drugs.
Computer-assisted molecular modelling techniques have been employed to develop receptor models for the phencyclidine (PCP) and sigma binding sites. The models differ in the position of the nitrogen atom, direction of the nitrogen-lone pair vector and in the location and nature of secondary binding groups. This study predicts the existence of distinct receptors for sigma and PCP ligands, and our receptor models can be used to design and predict the activity of drugs with PCP and/or sigma activity.
Manallack
D T
DT
University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Austin Hospital, Heidelberg, Victoria, Australia.
Beart
P M
PM
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D003196:Computer Graphics; D003986:Dibenzocycloheptenes / Q000378:metabolism; D016291:Dizocilpine Maleate; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D008968:Molecular Conformation; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma
D003986:Dibenzocycloheptenes; D007546:Isoquinolines; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C012134:SK&F 10047; C043564:LY 154045; D010620:Phenazocine; D010622:Phencyclidine