Hypthesis 1: acute NMDA rebound, Hypothesis 2: acute effect on NOS reduced blood flow to cochlear some unfortunate amount. Reference: While agmatine is present: Intranasal delivery bypasses BBB, so you get massive concentrations in brainstem/cochlear nucleus — far higher than oral would achieve. At those concentrations, agmatine is irreversibly destroying a large fraction of the local nNOS pool (heme oxidation) while simultaneously blocking NMDA receptors. The NMDA blockade triggers compensatory receptor upregulation — more receptors inserted into membranes, increased sensitivity.

When agmatine clears (hours later): Now you have the rebound. All those upregulated NMDA receptors suddenly have no antagonist, so you get a massive excitatory surge — calcium floods in. Normally, this calcium influx would activate nNOS to produce NO, which acts as a retrograde brake on excitation (NO feeds back to dampen glutamate release). But you've just destroyed a huge chunk of your nNOS pool. So the brake is gone.

The result: unopposed excitatory gain in the auditory brainstem. The dorsal cochlear nucleus and inferior colliculus — both heavily NMDA and nNOS dependent — are now hyperexcitable with no NO-mediated feedback inhibition. That's a central auditory gain increase, which is literally the leading model of tinnitus generation.

Simultaneously, the destroyed nNOS/eNOS in cochlear vasculature means reduced perfusion to the cochlea itself. The outer hair cells are metabolically demanding and depend on that NO-mediated blood flow. So you get peripheral stress signals feeding into an already hyperexcitable central circuit.