Allosteric modulators can be positive or negative effectors (PAMs or NAMs, respectively). PAMs increase the activity of the ligand, while NAMs block it (Figure 1).
Functional responses of allosteric modulators. Positive and negative allosteric modulators (positive allosteric modulators and negative allosteric modulators) may modulate the affinity and/or the efficacy of orthosteric agonists.
Serendipitously, the (4R,5S)-isomer (E1R) was discovered to interact at the sigma-1 receptor by increasing the binding affinity of an orthosteric ligand, which is characteristic of a PAM.