title: The real gordian knot: racemic mixtures versus pure enantiomers.
abstract: Many drugs exist as asymmetric three-dimensional (chiral) molecules and will therefore have several stereoisomers. There are often pharmacodynamic, pharmacokinetic and/or toxicological differences between enantiomers. The choice between developing a racemate or single enantiomers depends on therapeutic advances and developmental costs involved. Regarding the target environment for drug intervention, even if natural physiological mediators are achiral, their receptors may demonstrate a preference for the (-)- or (+)-enantiomer of agonists or antagonists. It is also obvious that the majority of enzymes and channels are stereospecific, at least to a variable extent. From a pharmacokinetics point of view, chirality can have an influence on drug absorption, distribution, metabolism and elimination. With a few exceptions, toxicological differences between isomers of known drugs are less dramatic than thought to be and only seldom substantiate the necessity of a racemic switch. The pharmaceutical industry is currently very interested in the so-called "racemic switch." Before proceeding to a racemic switch it is necessary to determine if 1) it is chemically feasible to produce a single enantiomer; 2) a clinical advantage is obtainable through a racemic switch; and 3) a marketing advantage is obtainable. The real goal of a racemic switch should be the rational development of compounds that are profitable for the company and--first of all--beneficial for the patient.
authors.affiliation: Pulmonary Pharmacology, Arzneimittelwerk Dresden, Radebeul, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Szelenyi
authors.forename: G
authors.initials: G
authors.lastname: Geisslinger
authors.forename: E
authors.initials: E
authors.lastname: Polymeropoulos
authors.forename: W
authors.initials: W
authors.lastname: Paul
authors.forename: M
authors.initials: M
authors.lastname: Herbst
authors.forename: K
authors.initials: K
authors.lastname: Brune