High-affinity binding of mequitamium iodide (LG 30435) to muscarinic and histamine H1 receptors

Eur J Pharmacol. 1990 Jul 17;182(3):413-20. doi: 10.1016/0014-2999(90)90038-8.

Abstract

Mequitamium iodide (LG 30435) is a novel quaternary ammonium phenothiazine with potential as an anti-asthmatic agent. In vitro binding experiments were performed in order to clarify the molecular mechanisms underlying its biological activity. Mequitamium iodide was found to bind with high affinity only to histamine H1 receptors in rat brain membranes (Ki = 9 nM) and to muscarinic acetylcholine receptors in various tissues homogenates (Ki = 12-77 nM) with no clearcut selectivity for any of the known subtypes. The interaction with muscarinic receptors in rat cerebral cortex and lung parenchyma was competitive, as showed by saturation studies. Lower affinity values (Ki = 1-10 microM) were found for serotonin 5-HT2, platelet-activating factor (PAF), verapamil and beta-adrenergic agents. These results indicate that both the potent antimuscarinic and antihistamine and the relatively weak anti-PAF pharmacological effects of mequitamium iodide may be explained by the direct interaction of the substance with the respective receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchodilator Agents / metabolism*
  • Cattle
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Guinea Pigs
  • In Vitro Techniques
  • Lung / drug effects
  • Lung / metabolism
  • Phenothiazines / metabolism*
  • Phenothiazines / pharmacology
  • Platelet Activating Factor / metabolism
  • Rabbits
  • Radioligand Assay
  • Rats
  • Receptors, Cholinergic / metabolism
  • Receptors, Histamine H1 / drug effects
  • Receptors, Histamine H1 / metabolism*
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism*
  • Trachea / metabolism

Substances

  • Bronchodilator Agents
  • Phenothiazines
  • Platelet Activating Factor
  • Receptors, Cholinergic
  • Receptors, Histamine H1
  • Receptors, Muscarinic
  • LG 30435