Table 1. Mechanisms of action observed by allosteric modulators.

Orthosteric Agonist	Binding of orthosteric agonists (which can be either endogenous neurotransmitters or synthetic agonists) to the neurotransmitter binding site induces a change in receptor confirmation and stabilizes an active state of the receptor.
Positive Allosteric Modulator (PAM)	PAMs bind to an allosteric site on the receptor that is distinct from the orthosteric binding pocket and increases the potency and/or efficacy of orthosteric agonists resulting in enhanced receptor activation when an orthosteric agonist is present.
Ago-PAM	Binding of Ago-PAMs alone is sufficient to induce receptor activation. In addition, these compounds increase the potency and/or efficacy of orthosteric agonists.
Orthosteric Antagonist	Binding of orthosteric antagonists have no effect on receptor activity. These compounds prevent activation of the receptor by preventing neurotransmitter binding.
Negative allosteric modulator (NAM)	NAMs bind to an allosteric site distinct from the orthosteric or neurotransmitter binding site and inhibit receptor activation via negative cooperativity to reduce the affinity and/or efficacy of orthosteric agonists.
Partial NAM	Partial NAMs do not completely block receptor activation, often due to weak negative cooperativity with respect to agonist binding. Accordingly, even when the allosteric binding pocket is fully occupied, partial NAMs will only partially reduce agonist responses.