1-（2,6-Dimethylphenoxy）-2-（3,4-dimethoxyphenylethylamino）-propane hydrochloride （DDPH） is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemiain vivo, and a rabbit model of isolated basilar arteriesin vitro. Our results show that DDPH （10 mg/kg） significantly increased hippocampal blood flowin vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in thein vitro rabbit model. DDPH （3 × 10–5 M） also inhibited histamine-stimulated extracellular calcium inlfux and intracellular calcium release. Our ifndings suggest that DDPH has a vasodilative effect bothin vivo andin vitro, which mediates a neuropro-tective effect on ischemic nerve tissue.
Objective To compare the inhibitory effects of DDPH(propranolol hydrochloride) on CYP2D and CYP3A in human liv...
Yin-Song Zhu,Xin-Xia Liu,Hui Chen Institute of Clinical Pharmacology,Tongji Medical College,Huazhong University of Science and Technology, Wuhan 430030
Aim and methods The study of three-dimensional quantitative structure-activity relationship （3D-QSAR） of DDPH and its derivatives has been performed using Apex-3D programme. Results The result indicates that substituents of para- and ortho-positions in phenyl ring of aryloxyalkylamine greatly influence the bioactivity. Conclusion The biophore model and 3D-QSAR equation help us not only further understand receptor-ligand interactions, but also design new compounds with better bioactivity.
