Possible Interaction: Gamma-Aminobutyric Acid and Ivermectin

“By revealing that ivermectin inhibits C. elegans muscle GABA and L-AChR receptors, our study adds two receptors to the already known ivermectin targets, thus contributing to the elucidation of its pleiotropic effects.”

“On simultaneous application of GABA and ivermectin the current amplitudes and the kinetics were determined by the agonist applied in the concentration eliciting the higher open probability.”

“ Ivermectin acts as a positive allosteric modulator of several Cys-loop receptors including the glutamate-gated chloride channels (GluCls), γ-aminobutyric acid receptors (GABAARs), glycine receptors (GlyRs), and neuronal α7-nicotinic receptors (α7 nAChRs).”

“ Ivermectin acts on the chloride-dependent channels of both glutamate and γ-aminobutyric acid , interrupting neurotransmission in invertebrates.”

“For example, ivermectin potentiated currents induced by GABA at the EC20 concentration in the unedited isoform but not in the fully edited variant.”

“In mammals, evidence indicates that IVM interacts with γ-aminobutyric acid (GABA)-mediated chloride channels.”

“ Ivermectin suppressed responses to GABA of RDLbdI/V, RDLbd and RDLbdI/VA301S.”

“The Hill coefficient was 1.52±0.45 for IVM and 0.34±0.56 for MOX (p<0.001), while the maximum … and MOX relative to GABA alone was 413.7±66.1 and 257.4±40.6%, respectively (p<0.05), showing that IVM causes … GABA action ….”

“ Ivermectin overdoses trigger severe neurologic signs by opening c-aminobutyric acid (GABA)-gated chloride channels, which in turn causes membrane hyperpolarization and blockade of neuronal impulses.”

“However, when coapplied with 10 µm GABA, ivermectin potentiated the GABA‐evoked current of the GAB‐1/HG1A receptor, but attenuated the GABA response of the GAB‐1/HG1E receptor.”