New drugs in the treatment
of stroke

Alfonso Losanno, *Fausto Passariello, Raffaele Carbone
ASL Caserta, *Centro Diagnostico

, Napoli

Up to recently, the stroke has not been considered a medical emergency simply because there were no safe therapies. The situation is now changing and a consistent amount of new experimental drugs is under evaluation.The starting point is the destructive process caused by ischaemia - a cascade of events leading to excessive glutamate and which inhibits the activation of enzymes able to destroy the cellular membranes and to cause damages induced by free radicals and nitric oxide. The drugs belonging to the group N-metil-D-aspartate (NMDA) interacting with glutamate receptors showed encouraging results.(ref. Bullock R., J. Neurosurgery, Oct. 96, 85/4).
However, this group of drugs is only one of the pharmaceutical choices to reduce the cytotoxic damages in the so-called "ischaemic penumbra". In this situation we still have 20 - 50 % of oxygen normal levels: this residual circulation gives the cells a survival margin, even though they are bound to die if the circulation will not be restored. At this point, we come to a new category of "fibrinogen depleting" drugs in the acute ischaemic attack such as the ancrod, extracted from agkistodon rhodostoma venom, and the batroxobin, extracted from bothrops moojeni (ref. Liu - Counsell - Wardlaw).
The acquisition of the agent actions of another active principle, the TGF B1, will be a further step ahead. TGF B1 is thought to play a decisive role in the angiogenesis as an effect of immunoreactions in the penumbra area (ref. Krupinski, Stroke, May 96). Also, great expectations are originated by the 21 aminosteroide Tirilazad mesylate, a peroxidation inhibitor of the lipid membrane. It is under evaluation as a possible cerebral protection in subarachnoid haemorrhage (ref. Hall, Eur J. Anaesthesiol, May 96, 13).
Finally, it must be mentioned the lubeluzole, which seems to be interfering with the effects of the nitric oxide, another ring of the ischaemic-cytotoxic cascade (ref. Diener HC, Stroke, Jan. 96, 27/1). Besides, it is under evaluation a new version of phenytoin (the famous Dicantin) e citicholine, the latter in particular seems to prevent the accumulation of free fatty acids.
We are now waiting for the results of the clinical trials undertaken everywhere around the world. Soon we forecast the appearing of new weapons to fight stroke occurrence.