Binding of the muscarine receptor antagonist heptane-1,7-bis(dimethyl-3'-phthalimidopropyl)ammonium bromide at cholinoceptor sites

Eur J Pharmacol. 1993 Jun 15;246(1):1-8. doi: 10.1016/0922-4106(93)90002-q.

Abstract

The binding of the bisquaternary muscarine receptor antagonist heptane-1,7-bis(dimethyl-3'-phthalimidopropyl)-ammonium bromide (C7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[3H]nicotine, [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate ([3H]QNB) in both central and peripheral tissues. C7/3-phth displayed an affinity for muscarine M2 receptors in rat atria (70.1 nM) which was 1.6-fold greater than for putative M4 receptors in rabbit lung, and 4- to 5-fold greater than for M1 receptors in rat cerebral cortex. Its affinity for nicotine receptors in the cortex was low, being 808-fold lower than its affinity for the M2 receptor. Although the displacement of (-)-[3H]nicotine and [3H]pirenzepine binding in rat cortex by C7/3-phth was best described in terms of one-site modelling, low Hill coefficients were observed with C7/3-phth in displacement studies using [3H]QNB in this tissue. The possibility of allosteric interactions or multiple receptor subtype interactions is discussed.

MeSH terms

  • Animals
  • Binding, Competitive
  • Bis-Trimethylammonium Compounds / metabolism*
  • Cerebral Cortex / metabolism
  • Female
  • In Vitro Techniques
  • Isoindoles
  • Kinetics
  • Lung / metabolism
  • Male
  • Muscarinic Antagonists*
  • Myocardium / metabolism
  • Nicotine / metabolism
  • Parasympatholytics / metabolism
  • Pirenzepine / analogs & derivatives
  • Pirenzepine / metabolism
  • Quinuclidinyl Benzilate / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Cholinergic / metabolism*

Substances

  • Bis-Trimethylammonium Compounds
  • Isoindoles
  • Muscarinic Antagonists
  • Parasympatholytics
  • Receptors, Cholinergic
  • heptane-1,7-bis(dimethyl-3'-phthalimidopropylammonium)
  • Pirenzepine
  • Quinuclidinyl Benzilate
  • Nicotine
  • otenzepad