As I understand it Sigma1 one agonists competes with any other in a winner take all fashion. Can both bind concurrently at different receptor locations?
My understanding is that there is one orthosteric binding site known and that the binding assays used to determine affinities would have assessed that known site only. IF that is true then it would be winner take all for a given receptor at a given point in time. That being said (and based on fuzzy pharmacology recall), over time and over huge numbers of available receptors the probability of binding at a given receptor at a given point in time would be determined by determined by relative binding affinities and disassociation constants. Specific probability determination is beyond my current ability without some remedial work...maybe someone else can describe more precisely.
For those more firmly rooted in pharmacology this would be a very basic issue and one I would expect AVXL would have answered for themselves very early on.
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