Pharmacology of Chiral Compounds 2-Arylpropionic Acid Derivatives

Authors: Landoni M.F.; Soraci A.

Source: Current Drug Metabolism, Volume 2, Number 1, March 2001 , pp. 37-51(15)

Publisher: Bentham Science Publishers

Abstract:

Molecules exist as three dimensional structures. Therefore they can exist in symmetrical and asymmetrical forms. Molecules with an asymmetric centre are chiral. If the molecule and its mirror image are non-superimposable, the relationship between the two molecules is enantiomeric and the two stereoisomers are enantiomers. Since enantiomers have very similar or identical physicochemical properties, it is very difficult to distinguish between them in an achiral environment. However, once in a chiral environment, as in the body, they exhibit clear differences. In fact, most of the physiological processes in nature are stereospecific. Stereospecificity can occur in pharmacokinetic processes, in particular that utilise a carrier protein, receptor or enzyme. In addition, stereoselectivity occurs in pharmacodynamic processes and the differences between enantiomers can be either qualitative and quantitative. 2-arylpropionic acid derivatives (2APAs - profens) are an important subgroup within the class of NSAIDs . These are chiral compounds marketed as racemic mixtures. Some members of the group in an species-dependent manner undergo a special type of metabolic transformation leading to partial inversion to the optical antipode through a specific conjugation with CoA (coenzyme A) and subsequent epimerization. This metabolic inversion has not only pharmacological consequences (related to clinical effect) but also toxicological consequences such as, formation of hybrid triglycerides and even inhibition of fatty acid ?-oxidation. Differences on inversion rate between compounds and species will be discussed as well as its modification by different patho-physiologic processes such as, inflammation.

Keywords: 2-Arylpropionic Acid Derivatives; NSAIDs; ESTEREOISOMERISM; ARYLPROPIONIC ACID DERIVA-TIVES; Plasma Protein Binding; Stereoselective metabolism; AcylCoA ligase; Racemase; Racemase; Hydrolase

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200013338810

Publication date: 2001-03-01

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

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• In this Subject: Anatomy & Physiology ,  Pharmacology
• By this author: Landoni M.F. ;  Soraci A.

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