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

Arzneimittelforschung. 1988 Aug;38(8):1075-8.

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.

Publication types

  • Comparative Study

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Binding Sites
  • Biogenic Monoamines / metabolism*
  • Brain / metabolism
  • Chemical Phenomena
  • Chemistry
  • Dopamine / metabolism
  • Norepinephrine / metabolism
  • Piperidines / metabolism*
  • Pyridines / metabolism
  • Rats
  • Receptors, Dopamine / metabolism
  • Receptors, GABA-A / metabolism
  • Receptors, Opioid / metabolism
  • Sensory Receptor Cells / metabolism*
  • Serotonin / metabolism
  • Synaptosomes / metabolism*

Substances

  • Biogenic Monoamines
  • Piperidines
  • Pyridines
  • Receptors, Dopamine
  • Receptors, GABA-A
  • Receptors, Opioid
  • Serotonin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine
  • Norepinephrine