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New effects of an antihistaminic against cerebral injury

December 15, 2004

Ranitidine, a widely used substance used as an antihistaminic drug against gastric ulcers, may become a new treatment for cerebral ischemia caused by craneoencephalic infarcts or traumatisms, the third leading cause of deaths in industrialised countries. In experiments with an model of cerebral ischemia using rats, a team from the Institute of Neurosciences of the Universitat Autònoma de Barcelona (Spain) has observed how the presence of ranitidine reduces neuronal death by a quarter. The substance reaches its maximum effect six hours after the lesion has occurred, which will facilitate treatment in real cases with humans.

The scientists of the Institute of Neurosciences at the UAB have studied ranitidine's effects on an experimental model using neurons from rats' brains. The cells underwent a lack of oxygen and glucose analogous to that which they suffer, within the brain, when there is a lack of blood flow (what happens when there is a cerebral ischemia) caused by an infarct or a traumatism. When a lesion of this type occurs, the cells either die directly or, in many cases, they becomes victims of a slow programmed death called apoptosis, a kind of "suicide" at a cellular level.

The researchers observed that ranitidine acts preferentially on the neurons that are in the process of apopotosis, and conclusively reduces the percentage of cells that die. Even when treatment is initiated six hours after the lack of oxygen and glucose, and maintaining it over a 24-hour period, this substance reduces by a quarter the number cells that die with respect to the number of cells that die when there is no treatment.

The fact that in the laboratory studies ranitidine's activity was optimal when administered hours after the lack of oxygen and glucose is highly important when looking towards a future use as treatment for cerebral ischemia in humans, in that, obviously, therapeutic treatments always take place after the time of the infarct or traumatism.

The authors of the research, recently published in Stroke magazine, affirm that the most immediate challenge is to verify the efficacy of the substance in in vivo experimental models of cerebral ischemia, because they have obtained good preliminar results with alive rats. Ranitidine is already widely used as a drug for treating gastric ulcers, which will accelerate the step towards clinical trials on humans. In fact, the researchers are already designing these clinical trails with associated universitary hospitals (Hospital Vall Hebron and Hospital de Sant Pau, in Barcelona).

The researchers also point out the need to work on designing new chemical compounds based on ranitidine that facilitate its administration, because the substance has difficulty moving from the blood flow to the brain. That is not an impediment in hospital interventions, as it can be administered directly to the brain, but to facilitate treatment it will be necessary to find a way in which the drug can be administered by oral route.

The following people participated in the research: Cristina Malagelada, Josefa Sabri'�, José Rodr'�guez, Xavier Xifr'� and Nahuai Badiola. They are all researchers at the Institute of Neurosciences and of the Biochemical Unit (Faculty of Medicine) of the Department of Biochemistry and of Molecular Biology at the UAB.

Barcelona, Universitat AutÃ�noma de

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