Agmatine has been discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and inactivated by agmatinase. Agmatine binds to α-adrenergic receptor and imidazoline receptor binding sites, and blocks NMDA receptors and other cation ligand-gated channels. However, while agmatine binds to α-adrenergic receptors, it exerts neither an agonistic nor antagonistic effect on these receptors, lacking any intrinsic activity. Short only of identifying specific ("own") post-synaptic receptors, agmatine fulfills Henry Dale's criteria for a neurotransmitter and is hence considered a neuromodulator and co-transmitter. The existence of theoretical agmatinergic-mediated neuronal systems has not yet been demonstrated although the existence of such receptors is implied by its prominence in the mediation of both the central and peripheral nervous systems. Research into agmatine-specific receptors and transmission pathways continues.
Due to its ability to pass through open cationic channels, agmatine has also been used as a surrogate metric of integrated ionic flux into neural tissue upon stimulation. When neural tissue is incubated in agmatine and an external stimulus is applied, only cells with open channels will be filled with agmatine, allowing identification of which cells are sensitive to that stimuli and the degree to which they opened their cationic channels during the stimulation period.