항 히스타민제의 H1 수용체와 무스카린 수용체에 대한 상대적 역가

Relative potency of antihistaminics for H1- and muscarinic receptors

The muscarinic antagonist l-[benzilic-4,4''-3H]quinuclidinyl benzilate([3H]QNB) bound to a single class of muscarinic receptor with high affinity in guinea pig ileal membranes. The KD and Bmax values for [3H]QNB calculated from analysis of saturation isotherms were 54pM and 156fmol/mg, respectively. H1-blockers inhibited [3H]QNB binding to ileal membranes with Ki values ranged from 0.008gM to 1.6mcM. The pseudo-Hill coefficients of HI-blockers for inhibition of [3H]QNB binding to the ileal membranes were close to unit. The Ki values for H1-blockers were similar to the Km values calculated by Schild plot of functional data obtained from inhibition of the carbachol-induced contraction in guinea-pig ileum, suggesting that binding of HI-blockers vs [3H]QNB in ileal membranes represents an interaction with a receptor of physiological relevance. The KH values of H1-blockers for H1-receptor estimated from inhibition of the histamine-induced contraction were the range of 0.15nM to 56.5nM. The KM/KH ratio of Hi-blockers varied over a wide range of 3 to 2300. Thus, the antihistaminic potencies of H1-blockers do not correlate with their antimuscarinic potencies, which suggest that antihistamines have different antimuscarinic potencies in therapeutic blood levels causing similar antiallergic effect. Among 13 traditional antihistaminics examined in this study, drug having the highest and the lowest KM/KH ratio is triprolidine and diphenidol, respectively. The present results demonstrate that the antimuscarinic property of antihistamines is not necessary for their antiallergic effect, and data on the affinity of antihistamines for musrinic and H1-receptors can be an important parameter in the selection and evaluation of these drugs.