Pharmacological profiles of opioid ligands at Kappa opioid receptors

Gharagozlou, Parham; Hashemi, Ezzat; DeLorey, Timothy M; Clark, J David; Lameh, Jelveh

doi:10.1186/1471-2210-6-3

BMC Pharmacology

Table 1 Binding affinity, potency, and intrinsic activity of opioid ligands in inhibiting adenylyl cyclase activity.

From: Pharmacological profiles of opioid ligands at Kappa opioid receptors

Ligands	EC₅₀ ± SEM (nM)	% Max Inhibition (Mean +/- SEM)	Relative Intrinsic activity	HEK-κ Ki (nM)
Butorphanol	57 ± 47	33 ± 7	0.57	2.5 ± 0.8
Cyclazocine	2 ± 2	39 ± 5	0.67	0.1 ± 0.0
Dezocine	Antagonist	---------	Antagonist	24.5 ± 1.5
Etorphine	0.4 ± 0.3	52 ± 4	0.90	ND
Fentanyl	1677 ± 917	58 ± 9	1.00	233 ± 33
Hydromorphone	279 ± 135	55 ± 6	0.95	55 ± 17
Lofentanil	153 ± 76	58 ± 6	1.00	8.2 ± 1.9
Metazocine	56 ± 13	47 ± 5	0.81	24 ± 7.5
Morphine	213 ± 137	55 ± 5	0.95	26 ± 3
Nalbuphine	2550 ± 1759	27 ± 7	0.47 *	6 ± 1
Nalorphine	483 ± 245	55 ± 7	0.95	1.6 ± 0.1
Naltrexone	Antagonist	--------	Antagonist	0.3 ± 0.1
SKF 10047	24 ± 6	38 ± 4	0.66	0.4 ± 0.2
Win 44441	Antagonist	--------	Antagonist	0.5 ± 0.2
Xorphanol	3.3 ± 2	49 ± 4	0.84	0.4 ± 0.2

Effective concentrations of opioid ligands in inhibiting forskolin-stimulated adenylyl cyclase activity were measured as described under "Materials and Methods". Data for EC₅₀'s represent the mean ± SEM obtained from two or more experiments carried out in duplicate. Maximum inhibition data represent the mean ± SEM obtained from the best fit curve for data from two or more experiments carried out in duplicate. All compounds denoted as antagonists completely reversed the effect of 1 nM etorphine. The effect of 1 nM etorphine in inhibiting cAMP production was 50–60% of maximum etorphine effect. Lofentanil and fentanyl had the highest intrinsic activity among the ligands tested. Relative intrinsic activity of the ligands were also compared to that of the putative endogenous ligand for κ-opioid receptor, dynorphin (EC₅₀ = 8 ± 2 nM, intrinsic activity = 52 ± 3%). All three ligands, lofentanil, fentanyl and dynorphin had similar intrinsic activity. The intrinsic activity of each ligand relative to fentanyl (designated as 1) and the endogenous ligand dynorphin was determined. Statistical significance was calculated for the inhibitory effect of each ligand in comparison to fentanyl and dynorphin. (*). Statistically significant difference (p < 0.05) relative to fentanyl or dynorphin suggested that the test ligand was a partial agonist compared to both reference ligands. The binding affinity of each ligand was measured by competition assays. The Ki for each ligand in denoted in the table.
ND = Not determined
* = p < 0.05

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