Characterization of the antimuscarinic effect of heptane-1,7-bis-(dimethyl-3'-phthalimidopropyl ammonium bromide)

Eur J Pharmacol. 1989 Mar 29;162(3):429-35. doi: 10.1016/0014-2999(89)90333-6.

Abstract

The effect of heptane-1,7-bis-(dimethyl-3'-phthalimidopropyl ammonium bromide) (C7/3'-phthalimidopropyl), an alkane bisquaternary compound with muscarinic receptor blocking activity was studied in guinea-pig atria and ileal longitudinal muscle. C7/3'-phthalimidopropyl was a more potent inhibitor of atrial muscarinic receptors, the cardioselectivity being ca. 32-fold. Previous studies in guinea-pig atria have shown that its antimuscarinic effect was of an allosteric nature. In ileal longitudinal muscle C7/3'-phthalimidopropyl (3 to 100 microM) appeared to behave in a competitive manner towards carbachol but the combination of atropine or homatropine with C7/3'-phthalimidopropyl produced a supra-additive inhibitory effect on the responses to carbachol. In both atria and ileal longitudinal muscle homogenates, C7/3'-phthalimidopropyl also slowed the dissociation rate of [3H]QNB suggesting an allosteric mechanism. In binding studies using either [3H]QNB or [3H]oxo-M, C7/3'-phthalimidopropyl recognized two binding sites in atria and ileum. In both tissues, C7/3'-phthalimidopropyl bound with high affinity (ca. 30-70 nM) to 60-85% of the sites and with low affinity (ca. 1-9 microM) to the remaining sites. Correlation of these affinity constants with the dissociation constants obtained in functional studies in the two tissues is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Binding, Competitive / drug effects
  • Bis-Trimethylammonium Compounds / pharmacology*
  • Guinea Pigs
  • Ileum / drug effects
  • In Vitro Techniques
  • Isoindoles
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Parasympatholytics / pharmacology*
  • Quinuclidinyl Benzilate
  • Tropanes / pharmacology

Substances

  • Bis-Trimethylammonium Compounds
  • Isoindoles
  • Parasympatholytics
  • Tropanes
  • heptane-1,7-bis(dimethyl-3'-phthalimidopropylammonium)
  • Quinuclidinyl Benzilate
  • Atropine
  • homatropine