The Selectivity of Drugs

1 Introduction. - 1. 1 What is Selectivity?. - 1. 2 The aims and accomplishments of Selectivity. - References. - 2 Three principles that control selectivity. - 3 Steps in the correlation of structure with biological activity. - 3. 1 Introduction. - 3. 2 The first correlations. - 3. 3 The concept of receptors'. - 3. 4 The receptor as an enzyme or permease. - 3. 5 The receptor as a nucleic acid. - 3. 6 The receptor as a coenzyme or other small molecule. - 3. 7 Other aspects of receptors. - 3. 8 Targets that are not necessarily receptors. - 3. 9 Regression analysis. - 3. 10 Conclusion. - References. - 4 Favourable differences in distribution: the first principle of selectivity. - 4. 1 Some examples. - 4. 2 Qualitative aspects of distribution. - 4. 3 Quantitative aspects of distribution. - 4. 4 The permeability of natural membranes. - 4. 5 Metabolic change leading to activation. - 4. 6 Metabolic change leading to inactivation. - 4. 7 Synergism and antagonism. - 4. 8 Conclusion. - References. - 5 Favourable differences in biochemistry: the second principle of selectivity. - 5. 1 Introduction. - 5. 2 Analogous enzymes. - 5. 3 More analogous enzymes: the dihydrofolate reductases. - 5. 4 Absence of enzymes from one of the species I. The sulphonamides and organophosphates. - 5. 5 Absence of enzymes. II Further examples. - 5. 6 Metabolite analogues (mostly antagonists). - 5. 7 Other utilizable biochemical differences. - 5. 8 Conclusion. - References. - 6 Favourable differences in cell structure: the third principle of selectivity. - References. - 7 Acquired resistance to drugs: the loss of selectivity. Language: English