[Innovative new approaches in pharmacology]. / Voies nouvelles d'innovations en pharmacologie.

After a brief recall of the molecular bases of the pharmacological actions, the two main ways of discovery of new drugs are described. On the one hand, the "deductive" approach starts with the elucidation of the pathogenic mechanisms and leads to selective drug designs for the appropriate receptors. The recent contributions of the molecular biology in this way are illustrated by some examples: "knock out" mice for the study of gene functions, discovery of new antibiotics thanks to genomic sequencing of bacteria, new pathogenic concepts about inflammation... On the other hand, the empirical approach is now grounded on two performant methods: High Throughput Screening and Combinatorial Chemistry which together have already given practical results. It is obvious that these two approaches are not opposite, but complementary.

[Cytochrome p450 and their implication in chemotherapy]. / Les cytochromes P450 et leurs implications en pharmacothérapie.

The hepatic cytochrome P450 enzymes (CYP450) play a prominent part in the metabolism of drugs, toxicants and some endogenous compounds. After a brief recall of their biochemical properties, the recent nomenclature is proposed. They are members of a large superfamily with various functions; the specialization of 3 families, CYP1, CYP2, CYP3 towards the metabolism of foreign and artificial compounds gives way to some evolutive considerations. Three main features are characteristic: these enzymes are poorly selective as a matter of substrates; some display genetic polymorphism; some are highly inducible. The mechanism of induction is detailed for CYP1A1. The consequences in pharmacotherapy are deduced: the CYP450 are the main cause of the variability in pharmacokinetics, of drug interactions and of drug adverse events of type II. Their implication in carcinogenesis, although controversial, deserves attention and requires further studies.

[Drug interactions involving psychotropic agents and anticonvulsants]. / Interactions médicamenteuses impliquant les agents psychotropes et les anticonvulsivants.

The problem of drug interactions is particularly important for psychoactive agents and for anticonvulsants because of their large use and of peculiarities of their clinical application. Such interactions may, in a few conditions, explain unforeseen adverse effects, and, more frequently, they disturb the meaning of plasma determinations of the monitored drugs. Some interactions can be pharmacokinetic, principally by way of enzyme induction or enzyme inhibition, and than they lead to disturbances in the plasma levels of the active substances. On the other hand, interactions can take place at the pharmacodynamic level, which is as an important condition although it is less well-known. Some examples are given for both mechanisms.

Hydroelectrolytic determination in paraplegics (total body water; exchangeable sodium and total body potassium).

Measurements of total body water and total exchangeable sodium, by isotopic dilution, and of total body potassium by whole body counting of the naturally occurring 40K isotope, were performed on stabilised paraplegic or tetraplegic subjects. Nineteen patients were investigated by the complete set of tests, six by only body counting. The results of total body potassium are expressed, following a uniform scale, as "relative values", which were established by the processing of reference values, from numberous paired healthy subjects.