Table 3.

Functional assay results for bifunctional peptide derivative ligands at opioid and Substance P receptors

No	Opioid agonist				Substance P antagonist
	MVD (δ)		GPI (μ)		GPI
	IC50 (nM)a	Emax (%)b	IC50 (nM)a	Emax (%)b	Ke (nM)c
1d	15 ± 2.0	100 ± 0	490 ± 29	92.5 ± 3.1	10 ± 2.1
2	14 ± 1.6	100 ± 0	460 ± 160	100 ± 0	10 ± 2.6
3	110 ± 21	100 ± 0	1900 ± 470	100 ± 0	2.8 ± 0.73
4	18 ± 4.9	100 ± 0	250 ± 48	100 ± 0	18 ± 6.0
5	13 ± 5.8	100 ± 0	520 ± 56	95.0 ± 2.9	1.8 ± 0.30
6	17 ± 4.3	100 ± 0	670 ± 134	93.7 ± 4.1	8.4 ± 1.0
Biphalin	2.7 ± 1.5		8.8 ± 0.3
DPDPEe	4.1		7300
DPDPEf	2.5		2720
L-732,138					250 ± 87

^aConcentration at 50% inhibition of muscle contraction at electrically stimulated isolated tissues (n = 4).

^bThe δ and μ opioid agonist efficacies (Emax values) of tested compounds were calculated using DPDPE and PL-017 as standards (Emax = 100 %) for MVD and GPI assays, respectively.

^cInhibitory activity against the Substance P induced muscle contraction in the presence of 1 μM naloxone, Ke: concentration of antagonist needed to inhibit Substance P to half its activity (n = 4).

^dReference.²⁰

^eReference.⁶²

^fReference.⁶³