Spongiform encephalopathies: a second chance for GABAergic agonists
Vamvakidès, A.
Annales Pharmaceutiques Francaises 56(1): 26-30
1998
ISSN/ISBN: 0003-4509 PMID: 9770032 Document Number: 495297
The risk of transmission of bovine spongiform encephalopathy (BSE) to humans and of a possible emergence, in the future, of an epidemic being seriously envisaged, a detection of the infection by the BSE prions is at present going well. On the other hand, recent neurochemical studies could suggest the triggering of an overstimulation of the brain GABAergic and glutamatergic systems after infection by the BSE prions. This overstimulation could, in the long-term (latency between the infection and the emergence of the clinical signs of the disease), lead to the destruction of the major inhibiting system (GABAergic) of the brain and the generalization of the neurotoxic processes. According to the above mentioned working hypothesis, it could be envisaged to use, immediately after the detection of the infection by the BSE prions, mixed GABAergic (A, B) agonists, selectively acting on the GABAergic autoreceptors and on the heteroreceptors situated on the glutamatergic terminals. Moreover these agonists could exhibit molecular characteristics (in terms of lipophilicity), which could operate in order to prevent the fixation of prions on the neuronal and astroglial membranes allowing their multiplication. According to the above mentioned criteria, mixed agonists Progabide and Gabalid or some GABA (B) agonists, with a relatively low affinity, could, actually, be the most interesting.