MECHANISTIC BASIS FOR THE DEVELOPMENT OF ANTIISCHEMIC DRUGS

The pharmacology of cerebral ischemia features 100 molecules and 20 potentially interesting mechanisms for preventing the tissue damage induced by anoxia-ischemia. The intricacy and complexity of the mechanisms involved probably account for the absence of definite evidence for effectiveness in man. The molecules which act on mechanisms qualifying as common denominators or triggering off cascade reactions, appear to be the best candidates. In this respect, the action of calcium, neurotransmitters, excitatory amino acids and pyrimidinergic or purinergic processes has to be given priority. Guidelines for the development of anti-ischemic molecules should be issued urgently, insisting on models, evaluation criteria, intervention timing and the parameters to be monitored (e.g. temperature, glycemia, choice of animal species).