Benzodiazepinas, reguladores alostéricos del receptor GABA-A: alcances fisiológicos, farmacológicos y terapéuticos / Benzodiazepines, allosteric modulators of GABA-A receptor: physiologic, pharmacologic and therapeutic features

RESUMO

The molecular basis underlying the anxiolytic, sedative hypnotic properties of the benzodiazepine compounds are examined at the ligh of recent progress in the field of psychopharmacology and molecular biology. The benzodiazepine receptors, originally characterized as the building site of radiolabelled benzodiazepines, are now identified as allosteric domains of a small population of the plethora of putative brain GABA-A receptor complexes. Emphasis is given to the understanding of the molecular biology of the GABA-A receptor complex and the hypothesis of the multiplicity of benzodiazepine receptors. Experiments describing the need of the gamma subunit of the GABA-A receptor for full benzodiazepine action as positive or negative allosteric modulators of the GABA-A receptor complez are analyzed. Likewise, experiments differentiating the barbiturate receptor from that of the benzodiazepines, alcohol and anesthetic agents are discussed ath the light of recent progress in the molecular biology of the GABA-A receptor. It is concluded that the GABA-A receptor complex is regulated at multiple sites, by a variety of drugs. Regarding putative endogenous ligands for the benzodiazepine receptor, evidences are discussed in support of the endozepines and their implications in health and diseases