Selecting appropriate techniques for meta-analysis.

In the 1950s Pfeiffer observed that the relative potencies of the enantiomers (mirror-image isomers) of several drugs appeared to be related to the dose of the racemate used clinically. The difference was greatest with the most active compounds and he suggested reasons for what has become known as 'Pfeiffer's rule'. In this short article Dick Barlow points out that there is a corollary to the rule - that the activity of the weaker enantiomer is determined by the activity of the more potent one - which is intuitively imporbable. With more examples and in a simpler situation, the picture is more complex and there are marked exceptions. The ideas behind Pfeiffer's rule overlook differences in molecular flexibility and there is a need for a revised model that takes entropy differences into account, particularly as recent developments in the elucidation of receptor structure are likely to revive interest in Pfeiffer's rule.

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