Correlation between absorption rates of beta-adrenoreceptor antagonists in rat small intestine and their molecular structures / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To study the correlation between the absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments and their molecular structural parameters.</p><p><b>METHODS</b>The net atomic charges and the molecular volumes of 11 beta-adrenoreceptor antagonists were obtained with the semiempirical self-consistent field molecular orbital calculation CNDO/2 method and Mont Carlo method respectively, using the minimum energy conformation obtained from the optimization of the standard molecular geometry with the molecular mechanics MM+ method. The stepwise multiple regression analysis was used to obtain the correlation equations.</p><p><b>RESULTS</b>The absorption rate constants of beta-adrenoreceptor antagonists in rat jejunum or ileum were well linearly correlated with the sum of the net charges of all hydrogen atoms and the molecular volumes. The beta-adrenoreceptor antagonist with higher lipophilicity, weaker hydrogen-bonding potential,and smaller molecular volume had greater absorption rate constants.</p><p><b>CONCLUSION</b>The absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments are mainly related with their lipophilicity,hydrogen-bonding potential and molecular size.</p>