nalfurafine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
10.1
|
pKd
|
124
|
|
⤷ |
pKd
10.1
[124]
|
ethylketocyclazocine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.4
|
pKd
|
116,136
|
|
⤷ |
pKd
9.4
[116,136]
|
enadoline
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
8.6 – 9.2
|
pKd
|
35
|
|
⤷ |
pKd
8.6 – 9.2
[35]
|
[3H]U69593
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
8.7 – 8.8
|
pKd
|
51,82,103
|
|
⤷ |
pKd
8.7 – 8.8
(Kd 2x10-9 – 1.6x10-9 M)
[51,82,103]
|
(-)-bremazocine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
10.5
|
pKi
|
116
|
|
⤷ |
pKi
10.5
[116]
|
ICI-199441
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
10.4
|
pKi
|
50
|
|
⤷ |
pKi
10.4
(Ki 4x10-11 M)
[50]
Description: Displacement of [3H]diprenorphine from human κ opioid receptor
|
dynorphin A
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
10.0 – 10.3
|
pKi
|
59,67
|
|
⤷ |
pKi
10.0 – 10.3
[59,67]
|
(-)-cyclazocine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
10.0
|
pKi
|
116
|
|
⤷ |
pKi
10.0
[116]
|
ethylketocyclazocine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
10.0
|
pKi
|
116
|
|
⤷ |
pKi
10.0
[116]
|
dynorphin A-(1-13)
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.3 – 10.7
|
pKi
|
82,116
|
|
⤷ |
pKi
9.3 – 10.7
[82,116]
|
butorphanol
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
9.9
|
pKi
|
24
|
|
⤷ |
pKi
9.9
(Ki 1.2x10-10 M)
[24]
Description: Displacement of [3H]U69593 from human κ opioid receptor expressed in CHO cells.
|
dynorphin A-(1-13)
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
9.9
|
pKi
|
67
|
|
⤷ |
pKi
9.9
[67]
|
dynorphin-(1-11)
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.7
|
pKi
|
116
|
|
⤷ |
pKi
9.7
[116]
|
etorphine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.7
|
pKi
|
116
|
|
⤷ |
pKi
9.7
[116]
|
GR 89696
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.7
|
pKi
|
89
|
|
⤷ |
pKi
9.7
[89]
|
enadoline
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.6
|
pKi
|
40,74
|
|
⤷ |
pKi
9.6
[40,74]
|
probe 1.1 [PMID: 24187130]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
9.6
|
pKi
|
134
|
|
⤷ |
pKi
9.6
(Ki 2.5x10-10 M)
[134]
|
dynorphin A
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
8.3 – 10.8
|
pKi
|
82,103,116,135-136
|
|
⤷ |
pKi
8.3 – 10.8
[82,103,116,135-136]
|
dynorphin B
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
9.5
|
pKi
|
67
|
|
⤷ |
pKi
9.5
[67]
|
U69593
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.5
|
pKi
|
51,116
|
|
⤷ |
pKi
9.5
[51,116]
|
naloxone benzoylhydrazone
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
9.5
|
pKi
|
116
|
|
⤷ |
pKi
9.5
[116]
|
MP1104
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
9.5
|
pKi
|
15
|
|
⤷ |
pKi
9.5
(Ki 3.3x10-10 M)
[15]
|
probe 2.1 [PMID: 24187130]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
9.5
|
pKi
|
134
|
|
⤷ |
pKi
9.5
(Ki 3.5x10-10 M)
[134]
|
α-neoendorphin
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
8.9 – 10.0
|
pKi
|
59,67
|
|
⤷ |
pKi
8.9 – 10.0
[59,67]
|
HS665
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.3
|
pKi
|
108
|
|
⤷ |
pKi
9.3
(Ki 4.9x10-10 M)
[108]
|
α-neoendorphin
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
8.3 – 10.2
|
pKi
|
103,135
|
|
⤷ |
pKi
8.3 – 10.2
[103,135]
|
β-neoendorphin
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
9.1
|
pKi
|
67
|
|
⤷ |
pKi
9.1
[67]
|
E2078
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
9.1
|
pKi
|
90
|
|
⤷ |
pKi
9.1
[90]
|
dynorphin B
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
8.1 – 9.9
|
pKi
|
82,103,116
|
|
⤷ |
pKi
8.1 – 9.9
[82,103,116]
|
spiradoline
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
9.0
|
pKi
|
16
|
|
⤷ |
pKi
9.0
[16]
|
asimadoline
|
|
|
|
|
|
|
|
|
|
|
Cp |
Agonist |
9.0
|
pKi
|
30
|
|
⤷ |
pKi
9.0
(Ki 1x10-9 M)
[30]
Description: Displacement of [3H]- 69593 from K opioid receptors from guinea pig cerebellum.
|
dynorphin A-(1-8)
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
8.0 – 9.9
|
pKi
|
82,103,116,129
|
|
⤷ |
pKi
8.0 – 9.9
[82,103,116,129]
|
ethylketocyclazocine
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
8.8
|
pKi
|
67
|
|
⤷ |
pKi
8.8
[67]
|
E2078
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
8.8
|
pKi
|
67
|
|
⤷ |
pKi
8.8
[67]
|
ICI 204448
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
8.8
|
pKi
|
16
|
|
⤷ |
pKi
8.8
[16]
|
tifluadom
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
8.8
|
pKi
|
136
|
|
⤷ |
pKi
8.8
[136]
|
U50488
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
7.8 – 9.7
|
pKi
|
14,82,103,116,123,135-136
|
|
⤷ |
pKi
7.8 – 9.7
[14,82,103,116,123,135-136]
|
cebranopadol
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
8.6
|
pKi
|
60
|
|
⤷ |
pKi
8.6
(Ki 2.6x10-9 M)
[60]
Description: Radioligand binding assay
|
hydromorphone
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
8.6
|
pKi
|
125
|
|
⤷ |
pKi
8.6
(Ki 2.8x10-9 M)
[125]
|
nalorphine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
7.9 – 9.1
|
pKi
|
116,136
|
|
⤷ |
pKi
7.9 – 9.1
[116,136]
|
U50488
|
|
|
|
|
|
|
|
|
|
|
Rn |
Partial agonist |
8.2 – 8.7
|
pKi
|
16,59,67
|
|
⤷ |
pKi
8.2 – 8.7
[16,59,67]
|
U69593
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
8.0 – 8.7
|
pKi
|
16,67
|
|
⤷ |
pKi
8.0 – 8.7
[16,67]
|
salvinorin A
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
7.8 – 8.7
|
pKi
|
11,94
|
|
⤷ |
pKi
7.8 – 8.7
[11,94]
|
BU08028
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
8.3
|
pKi
|
44
|
|
⤷ |
pKi
8.3
(Ki 5.63x10-9 M)
[44]
|
compound 3 [PMID: 23134120]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
8.2
|
pKi
|
108
|
|
⤷ |
pKi
8.2
(Ki 5.9x10-9 M)
[108]
|
(-)-pentazocine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
7.8 – 8.6
|
pKi
|
116,136
|
|
⤷ |
pKi
7.8 – 8.6
[116,136]
|
β-neoendorphin
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
7.9
|
pKi
|
103
|
|
⤷ |
pKi
7.9
[103]
|
tramadol
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
7.8
|
pKi
|
125
|
|
⤷ |
pKi
7.8
(Ki 1.4x10-8 M)
[125]
Description: Displacement of the kappa agonist U69593 from the kappa receptor expressed in CHO cells.
|
normorphine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
7.8
|
pKi
|
116
|
|
⤷ |
pKi
7.8
[116]
|
ADL5747
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
7.6
|
pKi
|
56
|
|
⤷ |
pKi
7.6
(Ki 2.5x10-8 M)
[56]
|
BW373U86
|
|
|
|
|
|
|
|
|
|
|
Rn |
Agonist |
7.5
|
pKi
|
12
|
|
⤷ |
pKi
7.5
(Ki 3.4x10-8 M)
[12]
|
nalbuphine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
7.4 – 7.5
|
pKi
|
136
|
|
⤷ |
pKi
7.4 – 7.5
[136]
|
ADL5859
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
7.4
|
pKi
|
55
|
|
⤷ |
pKi
7.4
(Ki 3.7x10-8 M)
[55]
|
carfentanil
|
|
|
|
|
|
|
|
|
|
|
Cp |
Agonist |
7.4
|
pKi
|
17
|
|
⤷ |
pKi
7.4
(Ki 4.31x10-8 M)
[17]
Description: Binding affinity- displacement of [3H]U69593 in guinea pig whole brain
|
morphine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
7.3
|
pKi
|
116
|
|
⤷ |
pKi
7.3
[116]
|
cebranopadol
|
|
|
|
|
|
|
|
|
|
|
Rn |
Agonist |
7.2
|
pKi
|
60
|
|
⤷ |
pKi
7.2
(Ki 6.4x10-8 M)
[60]
Description: Radioligand binding assay
|
β-endorphin
{Sp: Human}
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
6.3 – 7.9
|
pKi
|
103,116
|
|
⤷ |
pKi
6.3 – 7.9
[103,116]
|
dihydromorphine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
7.1
|
pKi
|
116
|
|
⤷ |
pKi
7.1
[116]
|
fentanyl
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
7.1
|
pKi
|
116
|
|
⤷ |
pKi
7.1
[116]
|
etonitazene
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
6.9
|
pKi
|
116
|
|
⤷ |
pKi
6.9
[116]
|
BW373U86
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
6.9
|
pKi
|
55
|
|
⤷ |
pKi
6.9
(Ki 1.3x10-7 M)
[55]
|
SCH221510
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
6.9
|
pKi
|
121
|
|
⤷ |
pKi
6.9
(Ki 1.31x10-7 M)
[121]
Description: Radioligand binding assay
|
morphine
|
|
|
|
|
|
|
|
|
|
|
Rn |
Partial agonist |
6.7 – 7.0
|
pKi
|
16,67
|
|
⤷ |
pKi
6.7 – 7.0
[16,67]
|
β-endorphin
{Sp: Human}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
6.8
|
pKi
|
67
|
|
⤷ |
pKi
6.8
[67]
|
UFP-512
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
6.7
|
pKi
|
122
|
|
⤷ |
pKi
6.7
[122]
Description: Measuring displacement of [3H]-diprenorphine in vitro
|
hydrocodone
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
6.6
|
pKi
|
75
|
|
⤷ |
pKi
6.6
(Ki 2.6x10-7 M)
[75]
|
(-)-methadone
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
6.5
|
pKi
|
116
|
|
⤷ |
pKi
6.5
[116]
|
DAMGO
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
6.5
|
pKi
|
116
|
|
⤷ |
pKi
6.5
[116]
|
SR16835
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
6.2
|
pKi
|
117
|
|
⤷ |
pKi
6.2
(Ki 6.813x10-7 M)
[117]
Description: Radioligand binding assay
|
bilorphin
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
6.1
|
pKi
|
21
|
|
⤷ |
pKi
6.1
(Ki 7.7x10-7 M)
[21]
|
[Leu]enkephalin
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
6.0
|
pKi
|
67
|
|
⤷ |
pKi
6.0
[67]
|
[Met]enkephalin
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Rn |
Full agonist |
6.0
|
pKi
|
67
|
|
⤷ |
pKi
6.0
[67]
|
DAMGO
|
|
|
|
|
|
|
|
|
|
|
Rn |
Partial agonist |
5.9
|
pKi
|
67
|
|
⤷ |
pKi
5.9
[67]
|
difelikefalin
|
|
|
|
|
|
|
|
|
|
|
Mm |
Agonist |
10.3
|
pEC50
|
99
|
|
⤷ |
pEC50
10.3
(EC50 4.8x10-11 M)
[99]
|
difelikefalin
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
9.8
|
pEC50
|
99
|
|
⤷ |
pEC50
9.8
(EC50 1.6x10-10 M)
[99]
|
HS665
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
8.4
|
pEC50
|
108
|
|
⤷ |
pEC50
8.4
(EC50 3.62x10-9 M)
[108]
Description: Measuring stimulation of [35S]GTPγS binding.
|
compound 3 [PMID: 23134120]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Partial agonist |
7.5
|
pEC50
|
108
|
|
⤷ |
pEC50
7.5
(EC50 3.5x10-8 M)
[108]
Description: Measuring stimulation of [35S]GTPγS binding.
|
probe 1.1 [PMID: 24187130]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Biased agonist |
5.4 – 7.5
|
pEC50
|
134
|
|
⤷ |
pEC50
7.5
(EC50 3.1x10-8 M)
[134]
Description: Measuring [35S]GTPγS binding
pEC50
5.4
(EC50 4.129x10-6 M)
[134]
Description: Measuring βarrestin2 recruitment
|
probe 2.1 [PMID: 24187130]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Biased agonist |
5.0 – 7.1
|
pEC50
|
134
|
|
⤷ |
pEC50
7.1
(EC50 8.47x10-8 M)
[134]
Description: Measuring [35S]GTPγS binding
pEC50
<5.0
(EC50 >1x10-5 M)
[134]
Description: Measuring βarrestin2 recruitment
|
α-neoendorphin
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
10.0
|
pIC50
|
128
|
|
⤷ |
pIC50
10.0
[128]
|
dynorphin B
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
10.0
|
pIC50
|
128
|
|
⤷ |
pIC50
10.0
[128]
|
dynorphin A-(1-8)
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.7
|
pIC50
|
128
|
|
⤷ |
pIC50
9.7
[128]
|
[D-Ala2,F5,Phe4]dynorphin-(1-17)-NH2
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.7
|
pIC50
|
128
|
|
⤷ |
pIC50
9.7
[128]
|
dynorphin-(1-17)-NH2
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.7
|
pIC50
|
128
|
|
⤷ |
pIC50
9.7
[128]
|
(-)-bremazocine
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.5
|
pIC50
|
128
|
|
⤷ |
pIC50
9.5
[128]
|
dynorphin A
{Sp: Human, Mouse, Rat}
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.4
|
pIC50
|
128
|
|
⤷ |
pIC50
9.4
[128]
|
[Met5]dynorphin-(1-17)
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.2
|
pIC50
|
128
|
|
⤷ |
pIC50
9.2
[128]
|
ethylketocyclazocine
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.0
|
pIC50
|
128
|
|
⤷ |
pIC50
9.0
[128]
|
U50488
|
|
|
|
|
|
|
|
|
|
|
Mm |
Partial agonist |
9.0
|
pIC50
|
128
|
|
⤷ |
pIC50
9.0
[128]
|
spiradoline
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
9.0
|
pIC50
|
128
|
|
⤷ |
pIC50
9.0
[128]
|
U69593
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
8.6
|
pIC50
|
128
|
|
⤷ |
pIC50
8.6
[128]
|
ICI 204448
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
8.2
|
pIC50
|
128
|
|
⤷ |
pIC50
8.2
[128]
|
[D-Ala2,F5,Phe4]dynorphin-(1-13)-NH2
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
7.7
|
pIC50
|
128
|
|
⤷ |
pIC50
7.7
[128]
|
β-endorphin
{Sp: Human}
|
|
|
|
|
|
|
|
|
|
|
Mm |
Partial agonist |
7.4
|
pIC50
|
128
|
|
⤷ |
pIC50
7.4
[128]
|
nalbuphine
|
|
|
|
|
|
|
|
|
|
|
Mm |
Full agonist |
7.4
|
pIC50
|
128
|
|
⤷ |
pIC50
7.4
[128]
|
pethidine
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
5.6
|
pIC50
|
87
|
|
⤷ |
pIC50
5.6
(IC50 2.37x10-6 M)
[87]
|
AR-M1000390
|
|
|
|
|
|
|
|
|
|
|
Hs |
Agonist |
5.1
|
pIC50
|
4
|
|
⤷ |
pIC50
5.1
(IC50 7.47x10-6 M)
[4]
|
[3H]enadoline
|
|
|
|
|
|
|
|
|
|
|
Hs |
Full agonist |
-
|
-
|
104
|
|
⤷ |
[104]
|