4,4-Diphenylpiperidine derivates and their sila analogues. A comparative study of their interaction with neural receptor biding sites and synaptosomal monoamine uptake.

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.