β-Alanine as a small molecule neurotransmitter

This review discusses the role of β-alanine as a neurotransmitter. β-Alanine is structurally intermediate between α-amino acid (glycine, glutamate) and γ-amino acid (GABA) neurotransmitters. In general, β-alanine satisfies a number of the prerequisite classical criteria for being a neurotransmitter: β-alanine occurs naturally in the CNS, is released by electrical stimulation through a Ca2+ dependent process, has binding sites, and inhibits neuronal excitability. β-Alanine has 5 recognized receptor sites: glycine co-agonist site on the NMDA complex (strychnine-insensitive); glycine receptor site (strychnine sensitive); GABA-A receptor; GABA-C receptor; and blockade of GAT protein-mediated glial GABA uptake. Although β-alanine binding has been identified throughout the hippocampus, limbic structures, and neocortex, unique β-alaninergic neurons with no GABAergic properties remain unidentified, and it is impossible to discriminate between β-alaninergic and GABAergic properties in the CNS. Nevertheless, a variety of data suggest that β-alanine should be considered as a small molecule neurotransmitter and should join the ranks of the other amino acid neurotransmitters. These realizations open the door for a more comprehensive evaluation of β-alanine's neurochemistry and for its exploitation as a platform for drug design.