Impact of species variability and ‘probe‐dependence’ on the detection and<i>in vivo</i>validation of allosteric modulation at the M₄muscarinic acetylcholine receptor

Abstract

These results provide evidence for species variability when comparing the allosteric interaction between LY2033298 and ACh at the M(4) mAChR, and also highlight how the interaction between LY2033298 and different orthosteric ligands is subject to 'probe dependence'. This has implications for the validation of allosteric modulator actions in vivo.