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This results from a tyramine-induced depletion of norepinephrine normally present in the readily releasable vesicle pool, and replacement of vesicular norepinephrine with tyramine (which functions as a false- or pseudo- neurotransmitter), which when released has no effect on postsynaptic adrenergic receptors (Figure 1)
In light of the on-target and off-target liabilities outlined above, we recommend a development path that prioritizes separation of lesion efficacy from systemic exposure
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