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GABA and glycine as neurotransmitters: a brief history

γ-Aminobutyric acid (GABA) emerged as a potentially important brain chemical just over 50 years ago, but its importance as a neurotransmitter was not fully recognized until more than 16 years later. Today, we know that at least 40% of inhibitory synaptic processing in the mammalian brain uses GABA.

Establishing its role as a transmitter has been a lengthy process, and with our current knowledge it seems hard to believe that there was ever any dispute about its role in the mammalian brain. The detailed information we now have about the receptors for GABA, along with the plethora of agents that facilitate or reduce GABA receptor mechanisms, make the prospects for further research very exciting.

The emergence of glycine as a transmitter appears to be relatively painless compared to GABA. Perhaps this is appropriate for the simplest of transmitter structures! Its discovery in the spinal cord and brainstem some 40 years ago was followed only 2 years later by the proposal to give it “neurotransmitter” status.

It took another 16 years before the receptor was biochemically isolated. Now it is readily accepted as a vital spinal and supraspinal inhibitory transmitter, and we know many details about its molecular structure and trafficking around neurons. The pharmacology of these receptors has lagged behind that of GABA. There is not the rich variety of allosteric modulators that we readily associate with GABA receptors and that has provided us with a virtual treasure trove of important drugs used for anxiety, insomnia, epilepsy, anesthesia, and spasticity, all of which are due to the action of the simple neutral amino acid GABA.

Nevertheless, the recognition that glycine receptors are involved in motor reflexes and nociceptive pathways, together with the recent emergence of drugs that exhibit some subtype selectivity, moves us a good deal closer to the goal of developing selective therapeutic ligands for the glycine receptor.

British Journal of Pharmacology: GABA and glycine as neurotransmitters: a brief history

Found at Alkohol adé (german)

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