title: 4,4-Diphenylpiperidine derivates and their sila analogues. A comparative study of their interaction with neural receptor biding sites and synaptosomal monoamine uptake.
abstract: The potential anti-Parkinson drugs 1-R-4,4-diphenylpiperidines and 1-R-4,4-diphenyl-4-sila-piperidines (R = H, CH3, i-propyl and t-butyl) were evaluated for their neuroreceptor affinity with respect to their structure-activity relationship. In these compounds substitution of the central carbon at position 4 by a silicon leads to more lipophilic substances. While the binding of these compounds to dopamine, serotonin and gamma-aminobutyric acid/benzodiazepine receptors is relatively non-specific, the binding to the mu- and delta-subtypes of opiate receptors and to the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine receptor binding site show probably pharmacologically relevant effects. In almost all cases the sila-compounds have a slightly higher receptor affinity than the corresponding carbon-compounds. The studies on the uptake sites for the biogenic amines noradrenaline, dopamine and serotonin, on the other hand, reveal some considerable differences between the carbon- and silicon-containing analogues. The 4,4-diphenyl-4-sila-piperidine has much stronger uptake inhibiting properties for noradrenaline and serotonin than the corresponding carbon compound.
authors.affiliation: Department of Neurology, University of Würzburg/Main, Fed. Rep. of Germany.
authors.forename: J P
authors.initials: JP
authors.lastname: Stasch
authors.forename: H
authors.initials: H
authors.lastname: Russ
authors.forename: U
authors.initials: U
authors.lastname: Schacht
authors.forename: M
authors.initials: M
authors.lastname: Witteler
authors.forename: D
authors.initials: D
authors.lastname: Neuser
authors.forename: M
authors.initials: M
authors.lastname: Gerlach
authors.forename: M
authors.initials: M
authors.lastname: Leven
authors.forename: W
authors.initials: W
authors.lastname: Kuhn
authors.forename: P
authors.initials: P
authors.lastname: Jutzi
authors.forename: H
authors.initials: H
authors.lastname: Przuntek
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001665:Binding Sites; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004298:Dopamine / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D010880:Piperidines; D011725:Pyridines; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D011957:Receptors, Opioid; D012701:Serotonin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D009638:Norepinephrine