Engineering a GABA endowed with pharmacological CNS activity when given by an extracerebral route

Joseph Vamecq 1 Yves Feutelais Pierre Maurois Mehrez Sghaier Emma Dichi Michèle German-Fattal Christine Herrenknecht Pierre Gressens Roméo Cecchelli 2 Lucie Dehouck 2, 3 James P. Stables Nicole Pagès 4 Bernard Legendre Pierre Bac
1 IMPRT - Institut de médecine predictive et de recherche thérapeutique
2 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
3 CELLIAL Technologies
4 Toxicologie
Abstract : Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter physiologically active in the central nervous system (CNS), being synthesised and delivered by GABAergic neurons. It is, however, pharmacologically devoid of CNS activity when presented externally to brain because of limited blood-brain barrier diffusion and intensive breakdown by astrocyte GABA transaminase. We show herein that extracerebral administration may be, however, pharmacologically effective in controlling experimental convulsive attacks when GABA is submitted to sublimation under vacuum just before use. Though initially enigmatic because nuclear magnetic resonance (NMR) and infrared (IR) analyses identified the sublimation-derived compound to be the reference zwitterionic GABA, this observation was understood by showing that the reference and sublimated GABAs were monoclinic and tetragonal phases of GABA solid, respectively.
Keywords : Gamma-aminobutyric acid (GABA) Tetragonal phase Monoclinic phase gauche conformer trans conformer Sublimation under vacuum
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Article dans une revue
Medicinal Chemistry Research, Springer Verlag, 2009, 18 (4), p. 255-267
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https://hal-univ-artois.archives-ouvertes.fr/hal-00545967
Contributeur : Wilfried Déplanques <>
Soumis le : lundi 13 décembre 2010 - 13:48:26
Dernière modification le : lundi 8 octobre 2018 - 17:44:04

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Joseph Vamecq, Yves Feutelais, Pierre Maurois, Mehrez Sghaier, Emma Dichi, et al.. Engineering a GABA endowed with pharmacological CNS activity when given by an extracerebral route. Medicinal Chemistry Research, Springer Verlag, 2009, 18 (4), p. 255-267. 〈hal-00545967〉

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