title: Rigid phencyclidine analogues. Binding to the phencyclidine and sigma 1 receptors.
abstract: Three phencyclidine (PCP) analogues possessing a highly rigid carbocyclic structure and an attached piperidine ring which is free to rotate were synthesized. Each analogue has a specific fixed orientation of the ammonium center of the piperidinium ring to the centrum of the phenyl ring. The binding affinities of the rigid analogues 1-piperidino-7,8-benzobicyclo[4.2.0]octene (14), 1-piperidinobenzobicyclo[2.2.1]heptene (16), and 1-piperidinobenzobicyclo[2.2.2]octene (13) for the PCP receptor ([3H]TCP) and th-receptor (NANM) were determined. The three analogues show low to no affinity for the PCP receptor but good affinity for the th-receptor and can be considered th-receptor selective ligands with PCP/th ratios of 13, 293, and 368, respectively. The binding affinities for the th-receptor are rationalized in terms of a model for the th-pharmacophore.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago 60607-7061, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Moriarty
authors.forename: L A
authors.initials: LA
authors.lastname: Enache
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: R
authors.initials: R
authors.lastname: Gilardi
authors.forename: M V
authors.initials: MV
authors.lastname: Mattson
authors.forename: O
authors.initials: O
authors.lastname: Prakash
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017478:Receptors, Phencyclidine / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000097605:Sigma-1 Receptor
chemical_list: D007202:Indicators and Reagents; D008024:Ligands; D010622:Phencyclidine; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor