[Simple derivatives of amino acid neurotransmitters. Anticonvulsant evaluation of derived amides, carbamates and esters of glycine and beta-alanine].
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.
Lambert
D M
DM
Départment des Sciences Pharmaceutiques Ecole de Pharmacie, Université catholique de Louvain, Bruxelles, Belgique.
Geurts
M
M
Scriba
G K
GK
Poupaert
J H
JH
Dumont
P
P
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000577:Amides; D000927:Anticonvulsants; D002219:Carbamates; D004952:Esters; D018377:Neurotransmitter Agents; D015091:beta-Alanine; D005998:Glycine
Dérivés simples d'acides aminés neurotransmetteurs. Evaluation anticonvulsivante de dérivés amides, carbamates et esters de la glycine et de la beta-alanine.