AM630 (iodopravadoline), a novel aminoalkylindole. AM630 behaved as a competitive antagonist of CP 55,940, WIN 55,212-2, anandamide and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (AM356), producing rightward shifts in the log concentration response curves of these cannabinoid receptor agonists. AM630 was markedly more potent as an antagonist of delta 9-THC and CP 55,940 (Kd = 14.0 and 17.3 nM respectively) than as an antagonist of WIN 55,212-2, AM356 or anandamide (Kd = 36.5, 85.9 and 278.8 nM respectively)[3]. AM630 is a protean ligand that can target a constitutively active form of the hCB(2) receptor (R*) with low affinity to produce agonism or neutral antagonism and a constitutively inactive form of this receptor (R) with much higher affinity to produce inverse agonism, and that the constitutive activity of whole cells is decreased less by pre-incubation with AM630 than with the higher-efficacy inverse agonist, SR144528[4]. AM251 and AM630 activated trigeminal (TG) sensory neurons in a concentration-dependent fashion (threshold 1 μM). AM630 (1-100 μM), but not AM251, was a significantly more potent agonist in cells co-expressing both TRPA1 and TRPV1 channels[5].
AM630 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCB2CHO cells
10 µM
24 hours
To investigate the ability of SR144528 to act as an inverse agonist in AM630-pre-incubated hCB2CHO cells. Results showed that SR144528 still exhibited inverse agonist activity in AM630-pre-incubated cells, but its maximal effect was significantly reduced.
Br J Pharmacol. 2012 Apr;165(8):2561-74
L02 liver cells
1 μg/mL
AM630 reversed the protective effect of GW on L02 cells.
Acta Pharmacol Sin. 2019 Nov;40(11):1404-1411.
mouse ventral tegmental area dopamine neurons
10 μM
10 min
AM630, as a selective CB2R antagonist, was used to block the enhancement of M-type K+ currents by JWH133. The results showed that AM630 completely abolished the enhancing effect of JWH133 on M-type K+ currents.
EBioMedicine. 2019 Apr;42:225-237.
RBL-2H3 cells
0.1 μM
15 min
AM630 antagonized the inhibitory effects of PEA on SP-induced degranulation and histamine release in RBL-2H3 cells
J Neuroinflammation. 2019 Dec 26;16(1):274.
Jurkat T cells
1 μg/mL, 2 μg/mL, 4 μg/mL
24 h
AM630 reversed GW-induced apoptosis of Jurkat T cells.
Acta Pharmacol Sin. 2019 Nov;40(11):1404-1411.
BeWo human choriocarcinoma cells
100 nM
24 h
AM630 completely abrogated AEA-mediated down-regulation of BCRP mRNA
Pharmacol Res. 2019 Mar;141:331-342.
AM630 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
MPTP-induced Parkinson's disease model
Intraperitoneal injection
20 μg/kg
Single administration
AM630 reversed the protective effects of JWH-133 and WIN55,212-2 on MPTP-induced degeneration of dopamine neurons, confirming the involvement of the CB2 receptor
Exp Mol Med. 2016 Jan 22;48(1):e205
Sprague-Dawley rats
Spinal cord ischemia reperfusion injury model
Intraperitoneal injection
1 mg/kg
1-hour pretreatment
AM630, as a CB2R antagonist, was used to reverse the effects of JWH-133. Results showed that AM630 pretreatment reversed the protective effects of JWH-133 on neurological function recovery and blood-spinal cord barrier.
J Neuroinflammation. 2020 Apr 6;17(1):101
C57BL/6 mice
Intramedullary fixation surgery model for tibial fracture
Intraperitoneal injection
3 mg/kg
Initiated immediately after recovery from anesthesia and repeated every 24 h postoperatively, lasting until postoperative day 7
To evaluate the effect of AM630 on postoperative cognitive function. Results showed that AM630 aggravated surgery-induced memory loss and increased the expression of proinflammatory factors in the hippocampus and prefrontal cortex.
J Neuroinflammation. 2017 Jul 19;14(1):138
BALB/c mice
Con A-induced acute liver injury model
Intraperitoneal injection
2 mg/kg
Single dose
AM630 reversed the protective effect of GW on Con A-induced acute liver injury.
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