Reversible and irreversible inhibition of rat brain muscarinic receptors is related to different substitutions on bisquaternary pyridinium oximes

Y. Kloog, R. Galron, D. Balderman, M. Sokolovsky

Research output: Contribution to journalArticlepeer-review

Abstract

The role of the functional substituents on the pyridinium ring of bisquaternary pyridinium compounds, mostly oximes, in exerting reversible and irreversible inhibition of binding of [3H]-N-methyl-4-piperidyl benzilate ([3H]-4NMPB) to rat brain stem muscarinic receptors was studied. The drugs tested, i.e. HGG-42, HGG-12, HGG-52, HI-6, obidoxim, SAD-128 and TMB-4, could reversibly inhibit binding of [3H]-4NMPB, with the highest potency (KI=1.7-6 μM) exhibited by analogs possessing hydrophobic substituents at position 3 or 4 of the pyridinium ring. Bisquaternary drugs possessing an oxime moiety at position 2, but not at position 4 of the pyridinium ring, could also induce about 30% reduction of maximal binding capacity (Bmax) (loss of muscarinic receptors) in addition to their reversible effect. Thus the structural correlates of the reversible and the irreversible effects of these drugs are different.

Original languageEnglish
Pages (from-to)37-39
Number of pages3
JournalArchives of Toxicology
Volume58
Issue number1
DOIs
StatePublished - Oct 1985

Keywords

  • Brain stem
  • Muscarinic receptor
  • Receptor inactivation
  • bisquaternary pyridinium oximes

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