Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors and as a neutral antagonist at 5-HT2C receptors. Agomelatine dose-dependently inhibits the firing of cells in the SCN (the endogeneous master clock) in Syrian hamsters (ED50 = 0.91 mg/kg, i.p.)[3]. In CSDS (chronic social defeat stress) mice treated 3 weeks with 50 mg/kg/d agomelatine, the anxious-like phenotype was not reversed, but the treatment successfully prevented the cognitive impairments and hippocampal gene expression modifications[4].
Agomelatine/阿戈美拉汀 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK-293 cells
10^-10 M
Evaluate the agonistic effect of agomelatine on MT1 and MT2 receptors and its antagonistic effect on 5-HT2C receptors
Br J Pharmacol. 2014 Aug;171(15):3604-19.
Agomelatine/阿戈美拉汀 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Depression model
Intraperitoneal injection
10-50 mg/kg
Once daily for 3 weeks
Evaluate the antidepressant effect of agomelatine and its antagonistic effect on 5-HT2C receptors
Br J Pharmacol. 2014 Aug;171(15):3604-19.
Wistar rats
LPS-induced depression model
Intraperitoneal injection
40 mg/kg
Once daily for 10 days
Agomelatine ameliorates LPS-induced depression-like behaviors, neuroinflammation, abnormal autophagy, and neuronal apoptosis by antagonizing the 5-HT2C receptor and upregulating the Gαi-2-cAMP-PKA pathway, thereby inhibiting the ASK1 pathway.
J Neuroinflammation. 2022 May 24;19(1):117
Rats
Depression model
Intraperitoneal injection
40 mg/kg/day
Once daily for 2 or 14 days
To investigate the effects of agomelatine on the electrical activity of dopamine, norepinephrine, and 5-HT neurons. Results showed that 2-day and 14-day administration of agomelatine increased the number of spontaneously active VTA-DA neurons and the firing rate of LC-NE neurons. After 14 days, agomelatine also increased the bursting activity of DA neurons, the firing rate of DRN-5-HT neurons, and the tonic activation of hippocampal 5-HT1A receptors.
Neuropsychopharmacology. 2013 Jan;38(2):275-84
New Zealand albino rabbits
Depression model
Oral
27,94 ± 5,50 ng/mL
Single dose
To evaluate the pharmacokinetics of agomelatine, showing a relative bioavailability enhancement of ≈7.25 folds for the transdermal system
Int J Nanomedicine. 2020 Nov 12;15:8893-8910
Rabbits
Transdermal
1 mg
Single dose
Evaluate the bioavailability of agomelatine microemulsion gel
Drug Deliv. 2017 Nov;24(1):1159-1169
Rats
Depression model
Intranasal administration
2.14 µg/g
Single dose, observation time 360 minutes
To evaluate the absolute bioavailability and brain targeting efficiency of Agomelatine. Results showed that intranasal administration of Agomelatine significantly increased Cmax and AUC in plasma and brain compared to oral administration, with absolute bioavailability of 37.89% and drug targeting efficiency index of 141.42.
Drug Deliv. 2017 Nov;24(1):1077-1085
New Zealand male albino rabbits
Enhanced IOP model
Ocular administration
0.02% w/v
Single dose, duration of 24 hours
Evaluation of the effect of Agomelatine on intraocular pressure, results showed the optimal bilosomal formula (OB) achieved a maximum % decrease in IOPmax of 82.682 ± 3.97% after 6 h, significantly higher than the Agomelatine solution (35.92 ± 2.8%).
Displacement of [125I]iodomelatonin form human MT1 receptor expressed in CHO cells after 120 mins, Ki=0.1 nM
22301214
CHO-Galpha16 cells
Function assay
20 mins
Binding affinity to rat MT1 receptor expressed in CHO-Galpha16 cells assessed as Ca2+ mobilization after 20 mins by FLIPR assay, EC50=2.1 nM
21237644
HEK 293
Function assay
Binding affinity for human Melatonin receptor type 1A stably transfected in human embryonic kidney cells (HEK 293) using 2-[125I]iodomelatonin as radioligand, Ki=6e-05 μM
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