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

Joseph Vamecq; Yves Feutelais; Pierre Maurois; Mehrez Sghaier; Emma Dichi; Michèle German-Fattal; Christine Herrenknecht; Pierre Gressens; Roméo Cecchelli; Lucie Dehouck; James P. Stables; Nicole Pagès; Bernard Legendre; Pierre Bac

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

Joseph Vamecq ^{1, 2, *} Yves Feutelais ^{3, 4} Pierre Maurois ⁵ Mehrez Sghaier ³ Emma Dichi Michèle German-Fattal ⁵ Christine Herrenknecht Pierre Gressens ⁶ Roméo Cecchelli ⁷ Lucie Dehouck ⁷ James P. Stables ⁸ Nicole Pagès ⁹ Bernard Legendre Pierre Bac ⁵

* Corresponding author

1 IMPRT - Institut de médecine predictive et de recherche thérapeutique

2 Pharmacologie de la mort neuronale et de la plasticité cérébrale

3 RTFSP - Remodelage tissulaire et fonctionnel : signalisation et physiopathologie

4 Groupe matériaux et santé

5 RTFSPP - Remodelage tissulaire et fonctionnel : signalisation et physio-pathologie

6 UPD7 - Université Paris Diderot - Paris 7

7 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique

8 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]

9 IUT Louis Pasteur [Université de Strasbourg, Schiltigheim]

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 : Sublimation under vacuum trans conformer Monoclinic phase gauche conformer Gamma-aminobutyric acid (GABA) Tetragonal phase

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Biochemistry, Molecular Biology

Complete list of metadatas

https://hal-univ-artois.archives-ouvertes.fr/hal-00545967
Contributor : Wilfried Déplanques <>
Submitted on : Monday, December 13, 2010 - 1:48:26 PM
Last modification on : Friday, September 13, 2019 - 1:13:44 AM

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

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

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