Disclosed herein are constitutively activated, non-endogenous versions of endogenous human G protein-coupled receptors comprising (a) the following amino acid sequence region (C-terminus to N-terminus orientation) and/or (b) the following nucleic acid sequence region (3' to 5' orientation) transversing the transmembrane-6 (TM6) and intracellular loop-3 (IC3) regions of the GPCR: (a) P.sup.1 AA.sub.15X and/or (b) p.sup.codon (AA-codon).sub.15 X.sub.codon, respectively. In a most preferred embodiment, P.sup.1 and P.sup.codon are endogenous proline and an endogenous nucleic acid encoding region encoding proline, respectively, located within TM6 of the non-endogenous GPCR; AA.sub.15 and (AA-codon).sub.15 are 15 endogenous amino acid residues and 15 codons encoding endogenous amino acid residues, respectively; and X and X.sub.codon are non-endogenous lysine and a non-endogenous nucleic acid encoding region encoding lysine, respectively, located within IC3 of the non-endogenous GPCR. Because it is most preferred that the non-endogenous human GPCRs which incorporate these mutations are incorporated into mammalian cells and utilized for the screening of candidate compounds, the non-endogenous human GPCR incorporating the mutation need not be purified and isolated per se (i.e., these are incorporated within the cellular membrane of a mammalian cell), although such purified and isolated non-endogenous human GPCRs are well within the purview of this disclosure.