[Simple derivatives of amino acid neurotransmitters. Anticonvulsant evaluation of derived amides, carbamates and esters of glycine and beta-alanine].
[Article in French]
Lambert DM, Geurts M, Scriba GK, Poupaert JH, Dumont P
Department des Sciences Pharmaceutiques Ecole de Pharmacie, Universite catholique de Louvain, Bruxelles, Belgique.
With GABA, glycine and beta-alanine are inhibitory amino acids. They
act mainly in the spinal cord and in the brain stem via the strychnine
sensitive glycine receptor. Glycine exhibits also a key rule in the excitatory
neurotransmission in the N-methyl-D-aspartate receptor complex. These two
hydrophilic molecules suffer from the lack of small neutral amino acid
carriers at the luminal side of the blood-brain barrier. The purpose of
this study is to design molecular entities able, by an enhanced lipophilicity,
to increase the pharmacological properties of these amino acids. From the
synthesis and from the anticonvulsant evaluation in the maximal electroshock
seizure test, we can underline: 1) In the case of a monosubstitution, a
N-substitution is more important than amidation or esterification of the
carboxylate. 2) Specially in the case of N-substitution, carbamates derivatives
are the most active compounds compared to the correspondent amides. N-benzyloxycarbonylglycine
is really attractive. The pharmacological properties, the tentative schedule
of the mode of action are presented too.
PMID: 7674119, UI: 95404422