کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2480187 1556172 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Species-specific lipophilicity of morphine antagonists
ترجمه فارسی عنوان
گونه های خاص لیپوفیز بودن مورفین آنتاگونیست ها
کلمات کلیدی
نوع لیپوپروتئین خاص ثابت پروتونهای میکروسکوپی، ضریب پارتیشن، نالوکسون، نالترکسون، آنتاگونیست های مورفین
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

Complete sets of microscopic acid–base and partition equilibrium constants were experimentally determined for therapeutically important morphine derivatives, including the widely used antagonists naloxone and naltrexone. The acid–base microequilibria were characterized by combining pH-potentiometry and deductive methods using synthesized auxiliary compounds. Microscopic protonation equilibria show that approximately three times as many zwitterionic microspecies than non-charged ones exist in oxymorphone and naltrexone solutions. On the other hand, the non-charged microspecies is the dominant one in the case of naloxone, although its concentration is only 1.34 times higher than that of its zwitterionic protonation isomer. Partition coefficients of the individual microspecies were determined by a combination of experimentally measured distribution constants and deductive methods. The contribution ratio of the non-charged versus zwitterionic species to the overall lipophilicity is quantified and depicted in terms of species-specific lipophilicities over the entire pH range for each compound. Our lipophilicity values allowed the molecular interpretation of the classical pharmacologic observation that naloxone has a faster onset for antagonist activity, and a concomitant shorter duration of action.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 78, 12 October 2015, Pages 1–7
نویسندگان
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