Fatty acid amide hydrolase (FAAH), an integral membrane bound enzyme and a member of the extensive family of serine hydrolases referred to as amidase signature (AS) family, catalyses degradation of lipid signalling fatty acid amides including the sleep-inducing oleamide and endogenous cannabinoid anandamide (AEA)[3]. BIA10-2474 is an inhibitor of fatty acid amide hydrolase (FAAH) with IC50 of 4.9 nM and shows IC50 values of 50-70 mg/kg (i.p.) in various rat brain regions[4]. BIA 10-2474 (50 mM) changed FAAH substrates (N-acylethanolamines), as well as several other lipid classes, including triglycerides, monoacylglycerols, (lyso) phosphatidylcholines, free fatty acids, and plasmalogens in human cortical neuron, which suggests BIA 10-2474 has the potential to cause metabolic dysregulation in the nervous system[5].
BIA 10-2474 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SW620 cells
0.2, 10, 50 μM
4 h or 24 h
Assess the inhibitory activity of BIA 10-2474 on various serine hydrolases
Science. 2017 Jun 9;356(6342):1084-1087
HEK293T cells
0.05–0.07 μM
4 h
Assess the inhibitory activity of BIA 10-2474 on FAAH
Science. 2017 Jun 9;356(6342):1084-1087
Rat brain membranes
1 nM to 10 μM
5 to 60 min
To evaluate the inhibitory effect of BIA 10-2474 on rat brain membrane FAAH. Results showed IC50 values of BIA 10-2474 decreased with pre-incubation time, reaching 398 nM at 60 minutes.
Br J Pharmacol. 2020 May;177(9):2123-2142
COS-7 cells expressing human FAAH
0.3 to 3000 nM
1, 3 or 24 h
To evaluate the inhibitory effect of BIA 10-2474 on human recombinant FAAH. Results showed IC50 values of BIA 10-2474 at 1, 3, and 24 hours were 74.4, 42.5, and 18.0 nM, respectively.
Br J Pharmacol. 2020 May;177(9):2123-2142
BIA 10-2474 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice (NMRI)
Normal mice
Oral
0.1 and 0.3 mg/kg
Single dose, evaluated at 1, 2, 4 and 8 hours post-dose
To evaluate the pharmacokinetics of BIA 10-2474 in mice. Results showed plasma and brain exposures of BIA 10-2474 were 33.0 ng/ml and 5.3 ng/g, respectively (0.1 mg/kg dose).
Br J Pharmacol. 2020 May;177(9):2123-2142
Rat
Sprague-Dawley rats
Intraperitoneal injection
0.5-5000 mg/kg
Single dose, 40 minutes prior
To evaluate the potency of BIA 10-2474 in inhibiting FAAH in rat brain, results showed BIA 10-2474 is a potent FAAH inhibitor with IC50 values of 50-70 mg/kg.
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