Neuronal nicotinic acetylcholine receptors (nAChRs) are members of the Cys-Loop ligand-gated ion channel superfamily, located both in the peripheral and central nervous systems (PNS and CNS, respectively)¹ and are validated therapeutic targets for various CNS pathologies². They can be divided into two main groups: those that contribute to receptors that are sensitive to the snake toxin α-Bungarotoxin (αBgt) and those that do not bind this toxin. Another important distinction is that the three αBgt-sensitive subunits (α7–9) can reconstitute functional homomeric receptors when expressed in a host system.

Positive allosteric modulators (PAMs) do not bind to the orthostetic binding sites but allosterically enhance the activity elicited by agonists by increasing the gating process (type I) and/or by decreasing desensitization (type II). Ivermectin is a positive allosteric modulator of the α7 neuronal nicotinic acetylcholine receptor; its prolonged pre-application to the neuronal nicotinic acetylcholine receptor α7 from human and chick results in potentiation of the acetylcholine-elicited current³. It is also a positive allosteric modulator of the purinergic P2X4 receptor⁴.

Ivermectin modulates glutamate- and GABA-activated Cl^- channels⁵ and probably binds to two sites on the GABAergic receptor resulting in activation of the receptor after binding to the high-affinity site and blocking it on further binding to the low-affinity site⁶. It also potentiates glycine-gated currents at low concentrations (30 nM)⁷.

Ivermectin was also found to positively modulate human P2X7 receptor while having no effect on the mouse receptor⁸.