Side effect pairing

Perhaps one of the most exciting new applications stems from the discovery in 1949 that small daily doses (l-2g) of LI2C03 taken orally provide an effective treatment for manic-depressive psychoses. The mode of action is not well understood but there appear to be no undesirable side effects. The dosage maintains the level of Li in the blood at about I mmol l and its action may be related to the influence of Li on the Na/K balance and (or) the Mg/Ca balance since Li is related chemically to both pairs of elements. 

The shape of a molecule has quite a bit to do with its reactivity. This is especially true in biochemical processes, where slight changes in shape in three-dimensional space might make a certain molecule inactive or cause an adverse side effect. One way to predict the shape of molecules is the valence-shell electron-pair repulsion (VSEPR) theory. The... 

The right-hand side of this equation is the first term of the density expansion of the radial distribution function which is valid only in the limit of low concentrations (p 0). For arbitrary concentrations, the radial distribution function defines the potential of the mean force w(r) by a similar equation to Eq. (47), where u(r) is substituted by w(r). In general, the potential of the mean force does not coincide with u(r) except in the limit of low concentrations. Therefore, a more general method to determine the effective pair potential should be developed. 

Methadone and most of its congeners possess a single chiral center and provide a rich field of examples of stereochemical selectivity in analgesics, with potency and morphinelike side effects residing mainly in one antipode of each enanliomorphic pair. Antipodal forms of methadone are best obtained... 

It is important to introduce two other terms that compare the pharmacological activity of a pair of enantiomers. The isomer imparting the desired activity is called the eu-tomer (in the case of Thalidomide this is the R-enantiomer), whereas the isomer which is inactive or causes unwanted side effects is called the distomer (this is the S-enantiomer for Thalidomide). Comparison of the potencies of the two isomers comes from the eudismic ratio and this can be used in vitro or in vivo. 

Because the ione pair of eiectrons of meiphaian (and other aromatic mustards) is iess reactive, there is a greater opportunity for distribution to cancer ceiis and a decreased incidence of severe side effects. There is a iower incidence of nausea and vomiting compared to mechiorethamine, but patients stiii experience myeiosuppression, which can ... 

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