A method for identifying and selecting a compound acting as an allosteric regulator of a GPCR-III is described. A method comparing the activity level of a recombinant GPCR-III (GPCR-III-.DELTA.), essentially depleted of the extracellular domain of the corresponding native GPCR-III, in the presence of a given compound, with the activity level of the same GPCR-III-.DELTA. is described. A method of identifying positive or negative allosteric regulators of GPCRs-III is described.