Renzetti A R, Barone D, Criscuoli M
Department of Pharmacology, Laboratori Guidotti S.p.A., Pisa, Italy.
Eur J Pharmacol. 1990 Jul 17;182(3):413-20. doi: 10.1016/0014-2999(90)90038-8.
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.
碘化甲喹铵（LG 30435）是一种新型季铵类吩噻嗪，具有作为抗哮喘药物的潜力。为了阐明其生物活性的分子机制，进行了体外结合实验。发现碘化甲喹铵仅与大鼠脑膜中的组胺H1受体（Ki = 9 nM）和各种组织匀浆中的毒蕈碱型乙酰胆碱受体（Ki = 12 - 77 nM）具有高亲和力结合，对任何已知亚型均无明显选择性。如饱和研究所示，其与大鼠大脑皮质和肺实质中毒蕈碱受体的相互作用具有竞争性。对于5-羟色胺5-HT2、血小板活化因子（PAF）、维拉帕米和β-肾上腺素能药物，发现其亲和力值较低（Ki = 1 - 10 μM）。这些结果表明，碘化甲喹铵强大的抗毒蕈碱和抗组胺作用以及相对较弱的抗PAF药理作用可能是该物质与相应受体直接相互作用的结果。
