Glycine

Glycine is the simplest amino acid by structure, and in the nervous system it carries two distinct and equally important roles: it acts as an inhibitory neurotransmitter in the spinal cord and brainstem, and it serves as a required co-agonist at NMDA-type glutamate receptors throughout the brain.

Both roles shape how neurons fire. The inhibitory role governs motor control and sensory gating at the spinal level; the co-agonist role means glycine availability partly determines whether NMDA receptors can open at all. Understanding one molecule in two jobs is central to making sense of a wide range of psychoactive substances.

How it works · its role

As an inhibitory transmitter, glycine binds to glycine receptors — ion channels that, when open, allow chloride to flow into the neuron. This influx makes the cell harder to excite, suppressing firing. The mechanism parallels that of GABA, and both inhibitory systems run in parallel across the central nervous system.

At NMDA receptors, glycine's role is structurally different. The NMDA receptor carries a dedicated co-agonist binding site — separate from where glutamate binds — and the channel cannot open unless both sites are occupied simultaneously. In most brain regions, glycine is thought to keep this site largely saturated, setting a background level of NMDA readiness that other factors then modulate.

Relevance to substances & effects

NMDA antagonists — ketamine, phencyclidine (PCP), dextromethorphan (DXM) — act by physically blocking the NMDA receptor channel. Because glycine is a required co-agonist at that same receptor, it is a direct participant in the signalling system these substances disrupt. Dissociation, perceptual distortion, analgesia, and the dream-like quality of high-dose ketamine all trace substantially to NMDA receptor inhibition, making glycine tone a background variable in how those effects arise.

Ethanol enhances inhibitory glycine receptor signalling in the spinal cord, and this is one mechanism behind its characteristic slowing of reflexes and motor coordination — effects distinct from its actions on GABA.

Strychnine, a plant-derived convulsant, works by selectively blocking glycine receptors, producing uncontrolled muscular excitation. It is a stark illustration of how critical inhibitory glycine signalling is to normal motor function, and why loss of that signalling is dangerous.