Rigid phencyclidine analogues. Binding to the phencyclidine and sigma 1 receptors.
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.
Moriarty
R M
RM
Department of Chemistry, University of Illinois at Chicago 60607-7061, USA.
Enache
L A
LA
Zhao
L
L
Gilardi
R
R
Mattson
M V
MV
Prakash
O
O
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
D007202:Indicators and Reagents; D008024:Ligands; D010622:Phencyclidine; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor