Agomelatine for the treatment of generalized anxiety disorder

Buoli, Massimiliano; Grassi, Silvia; Serati, Marta; Altamura, Alfredo Carlo

doi:10.1080/14656566.2017.1359257

Cited by 50 publications

(29 citation statements)

References 54 publications

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“…This drug also has noteworthy therapeutic efficacy for the treatment of generalized anxiety disorder [12]. It has a unique pharmacological mechanism by having agonistic effects on melatonergic MT 1 and MT 2 receptors, but antagonistic effects on serotonergic 5-HT 2C receptors [13,14].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Can

Üçel

Özkay

et al. 2018

IJMS

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Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1–3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials.

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Section: Introductionmentioning

confidence: 99%

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Can

Üçel

Özkay

et al. 2018

IJMS

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“…Those compounds can be regarded as reference melatonergic ligands. Figure 1 depicts structures of the seven main compounds listed on the IUPHAR website including the natural agonist, melatonin; the radiotracer (a super‐agonist: 2‐iodomelatonin); two antagonists or partial agonists (4P‐PDOT & luzindole) 19,128 ; and three compounds that are being marketed for delayed sleep onset (Ramelteon, Rozerem ® ), 129 depression (Agomelatin, Valdoxan ® ), 130 or non‐24 hour sleep‐wake disorder (Tasimelteon, Hetlioz ® ) 131 …”

Section: Reference Moleculesmentioning

confidence: 99%

Melatonin receptor ligands: A pharmaco‐chemical perspective

Boutin

Witt‐Enderby

Sotriffer

et al. 2020

Journal of Pineal Research

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Melatonin MT1 and MT2 receptor ligands have been vigorously explored for the last 4 decades. Inspection of approximately 80 publications in the field revealed that most melatonergic ligands were structural analogues of melatonin combining three essential features of the parent compound: an aromatic ring bearing a methoxy group and an amide side chain in a relative arrangement similar to that present in melatonin. While several series of MT2‐selective agents—agonists, antagonists, or partial agonists—were reported, the field was lacking MT1‐selective agents. Herein, we describe various approaches toward the development of melatonergic ligands, keeping in mind that most of the molecules/pharmacophores obtained were essentially melatonin copies, even though diverse tri‐ or tetra‐cyclic compounds were explored. In addition to lack of structural diversity, only few studies examined the activity of the reported melatonergic ligands in vivo. Moreover, an extensive pharmacological characterization including biopharmaceutical stability, pharmacokinetic properties, specificity toward other major receptors to name a few remained scarce. For example, many of the antagonists described were not stable in vivo, were not selective for the melatonin receptor subtype of interest, and were not fully characterized from a pharmacological standpoint. Indeed, virtual screening of large compound libraries has led to the recent discovery of potent and selective melatonin receptor agonists and partial agonists of new chemotypes. Having said this, the melatonergic field is still lacking subtype‐selective melatonin receptor antagonists “active” in vivo, which are critical to our understanding of melatonin and melatonin receptors’ role in basic physiology and disease.

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“…It seems, therefore, interesting to find out the effects of chronic treatment with the novel antidepressant and antianxiety drug agomelatine [16][17][18][19] on liver cytochrome P450 at normal conditions and under CMS, with reference to the model antidepressant imipramine.…”

Section: Introductionmentioning

confidence: 99%

The effects of agomelatine and imipramine on liver cytochrome P450 during chronic mild stress (CMS) in the rat

et al. 2020

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Background The aim of our research was to determine the effects of chronic treatment with the atypical antidepressant agomelatine on the expression and activity of liver cytochrome P450 (CYP) in the chronic mild stress (CMS) model of depression, and to compare the results with those obtained for the first-generation antidepressant imipramine. Methods Male Wistar rats were subjected to CMS for 7 weeks. Imipramine (10 mg/kg ip/day) or agomelatine (40 mg/kg ip/day) was administered to nonstressed or stressed animals for 5 weeks (weeks 3–7 of CMS). The levels of cytochrome P450 mRNA, protein and activity were measured in the liver. Results Agomelatine and imipramine produced different broad-spectrum effects on cytochrome P450. Like imipramine, agomelatine increased the expression/activity of CYP2B and CYP2C6, and decreased the CYP2D activity. Unlike imipramine, agomelatine raised the expression/activity of CYP1A, CYP2A and reduced that of CYP2C11 and CYP3A. CMS modified the effects of antidepressants at transcriptional/posttranscriptional level; however, the enzyme activity in stressed rats remained similar to that in nonstressed animals. CMS alone decreased the CYP2B1 mRNA level and increased that of CYP2C11. Conclusion We conclude the following: (1) the effects of agomelatine and imipramine on cytochrome P450 are different and involve both central and peripheral regulatory mechanisms, which implicates the possibility of drug–drug interactions; (2) CMS influences the effects of antidepressants on cytochrome P450 expression, but does not change appreciably their effects on the enzyme activity. This suggests that the rate of antidepressant drug metabolism under CMS is similar to that under normal conditions.

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Agomelatine for the treatment of generalized anxiety disorder

Cited by 50 publications

References 54 publications

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Melatonin receptor ligands: A pharmaco‐chemical perspective

The effects of agomelatine and imipramine on liver cytochrome P450 during chronic mild stress (CMS) in the rat

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