LOOKING FOR NEW DRUGS - WHAT CRITERIA

How to look for new drugs? What guideines to use? Have we to continue investigations on plant and marine organisms? These questions arise frequently today. A pharmacological effect results from the addition of many effects at a molecular level, i.e., the interaction between a ligand and a receptor. As long as the chemical structure of this receptor remains unknown, studies of Nature's resources will yield the largest reservoir of new drugs. Nature provides our imagination with the pattern of novel biologically active molecules. Criteria classically used in the past to select plants for study were chemotaxonomy, ethnopharmacology or pharmacotaxonomy. Examples will be taken from personal experience, to illustrate work done according to the chemotaxonomical approach (Ochrosia and ellipticines), and the ethnopharmacological approach (antiinflammatory properties of Euphorbiaceae from New Caledonia). Taking into account that one of the major problems we have to face is the unsatisfactory classical pharmacological testing procedure, we have tried to set up a network grouping biologists and chemists. Among many results obtained, one concerns the use of the mammalian hypothalamo-pituitary system to screen effects of alkaloids extracted from Psychotria oleoides, a Rubiceae collected in New Caledonia. Psycholeine exhibits an intriguing activity on GH release. Another result concerns the influence of a Labiatae extract on the adenylate cyclase system: 9 HODE extracted from Glechoma hederacea stimulates the basal level of enzyme activity in platelets, this activity being possibly involved in the folk uses claimed. Using the tubulin test to screen antimitotic activities of plant extracts, the biological activity of rhazinilam has been demonstrated as responsible for the antitubulin activity of a Malaysian plant, Kopsia singapurensis. From past experience, it seems important to improve pharmacological screening methods and to have on hand, as close as possible to the field, some simple in vitro biological procedures allowing a better selection of interesting compounds.