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The review would benefit from a bit more text on how this notion impacts the balance between desired therapeutic effects, "diluted" effects from dimer-mediated versus non-dimer effects, and undesired off-target effects (which are discussed some in terms of receptor specificity, but not in terms of anatomy, where the same dimer may have different effects in different brain regions). Response: We have added a new section title General treatment approaches before the concluding remarks

10.1016/s0140-6736(70)91347-4 Lancet 177 StinsonL

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