阿戈美拉汀對癲癇共病偏頭痛患者的治療潛力_Journal of Epilepsy

Authors：

吳玉嬌 ^1,2 , 姜荊 ^1,2 ,  劉學伍 ^1,2

1. ;
2. ;

Corresponding?author：

劉學伍, Email: snlxw1966@163.com

Keywords：

阿戈美拉汀; 癲癇; 偏頭痛; 睡眠

DOI：

10.7507/2096-0247.202206002

Video：

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Abstract Full text Figures/Tables Video References Cited by

與一般人群相比，癲癇患者偏頭痛的患病率通常高于正常水平，反之亦然。偏頭痛和癲癇也具有更高的焦慮和抑郁的患病率和發生率。神經元網絡的過度興奮是偏頭痛和癲癇的共同病理機制。睡眠障礙可以導致癲癇及頭痛的發生。褪黑激素（Melatonin，MT）是松果體分泌的一種內源性激素，具有晝夜節律特性，在癲癇中具有重要作用。作為MT1和MT2受體激動劑以及 5-羥色胺2C（5- Hydroxytryptamine 2C，5-HT2C）受體拮抗劑，阿戈美拉汀是一種新型抗抑郁藥，其具有改善晝夜節律、減少去極化導致的谷氨酸釋放、強大的神經保護作用、抗炎及可能的抗氧化特性可能使其成為治療癲癇共病偏頭痛的潛在藥物。

Citation： 吳玉嬌, 姜荊, 劉學伍. 阿戈美拉汀對癲癇共病偏頭痛患者的治療潛力. Journal of Epilepsy, 2022, 8(5): 431-435. doi: 10.7507/2096-0247.202206002 Copy

1.	Zhu L, Chen L, Xu P, et al. Genetic and molecular basis of epilepsy-related cognitive dysfunction. Epilepsy Behav, 2020, 104(Pt A): 106848.
2.	Gotra P, Bhardwaj N, Ludhiadch A, et al. Epilepsy and migraine shared genetic and molecular mechanisms: focus on therapeutic strategies. Mol Neurobiol, 2021, 58(8): 3874-3883.
3.	Mantegazza M, Cestele S. Pathophysiological mechanisms of migraine and epilepsy: similarities and differences. Neurosci Lett, 2018, 667: 92-102.
4.	Terrone G, Balosso S, Pauletti A, et al. Inflammation and reactive oxygen species as disease modifiers in epilepsy. Neuropharmacology, 2020, 167: 107742.
5.	Chumboatong W, Khamchai S, Tocharus C, et al. Agomelatine exerts an anti-inflammatory effect by inhibiting microglial activation through TLR4/NLRP3 pathway in pMCAO rats. Neurotox Res, 2022, 40(1): 259-266.
6.	Alcocer-Gomez E, Casas-Barquero N, Williams MR, et al. Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in major depressive disorder. Pharmacol Res, 2017, 121: 114-121.
7.	Long R, Zhu Y, Zhou S. Therapeutic role of melatonin in migraine prophylaxis: a systematic review. Medicine (Baltimore), 2019, 98(3): e14099.
8.	Dehdashtian E, Hosseinzadeh A, Hemati K, et al. Anti-convulsive effect of thiamine and melatonin combination in mice: involvement of oxidative stress. Cent Nerv Syst Agents Med Chem, 2021, 21(2): 125-129.
9.	Hosseinzadeh A, Dehdashtian E, Jafari-Sabet M, et al. The effects of vitamin D3 and melatonin combination on pentylenetetrazole-induced seizures in mice. Cent Nerv Syst Agents Med Chem, 2022, [Epub ahead of print].
10.	Rocha A, de Lima E, Amaral F, et al. Altered MT1 and MT2 melatonin receptors expression in the hippocampus of pilocarpine-induced epileptic rats. Epilepsy Behav, 2017, 71(Pt A): 23-34.
11.	Akkaya R, Gumus E, Akkaya B, et al. Wi-Fi decreases melatonin protective effect and increases hippocampal neuronal damage in pentylenetetrazole induced model seizures in rats. Pathophysiology, 2019, 26(3-4): 375-379.
12.	Wan L, Yang G, Sun Y, et al. Combined melatonin and adrenocorticotropic hormone treatment attenuates N-methyl-d-aspartate-induced infantile spasms in a rat model by regulating activation of the HPA axis. Neurosci Lett, 2021, 748: 135713.
13.	Peled N, Shorer Z, Peled E, et al. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia, 2001, 42(9): 1208-1210.
14.	Verma N, Maiti R, Mishra BR, et al. Effect of add-on melatonin on seizure outcome, neuronal damage, oxidative stress, and quality of life in generalized epilepsy with generalized onset motor seizures in adults: a randomized controlled trial. J Neurosci Res, 2021, 99(6): 1618-1631.
15.	Yalyn O, Arman F, Erdogan F, et al. A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures. Epilepsy Behav, 2006, 8(3): 542-526.
16.	Yahyavi-Firouz-Abadi N, Tahsili-Fahadan P, Riazi K, et al. Involvement of nitric oxide pathway in the acute anticonvulsant effect of melatonin in mice. Epilepsy Res, 2006, 68(2): 103-113.
17.	Albertson TE, Peterson SL, Stark LG, et al. The anticonvulsant properties of melatonin on kindled seizures in rats. Neuropharmacology, 1981, 20(1): 61-66.
18.	Moezi L, Shafaroodi H, Hojati A, et al. The interaction of melatonin and agmatine on pentylenetetrazole-induced seizure threshold in mice. Epilepsy Behav, 2011, 22(2): 200-206.
19.	Banach M, Gurdziel E, Jedrych M, et al. Melatonin in experimental seizures and epilepsy. Pharmacol Rep, 2011, 63(1): 1-11.
20.	Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, et al. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol, 2012, 351(2): 152-166.
21.	Krishnakumar A, Nandhu MS, Paulose CS. Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri. Epilepsy Behav, 2009, 16(2): 225-230.
22.	Silenieks LB, Carroll NK, Van Niekerk A, et al. Evaluation of selective 5-HT2C agonists in acute seizure models. ACS Chem Neurosci, 2019, 10(7): 3284-3295.
23.	Victor Petersen A, Perrier JF. Serotonin prevents temporal lobe epilepsy by inhibiting bursting neurons from the subiculum. Med Sci (Paris), 2017, 33(8-9): 727-729.
24.	Demirel EA, Erdogan MA, Cinar BP, et al. The reducing effect of agomelatine on pentylenetetrazol-induced convulsions. Biol Futur, 2019, 70(4): 336-340.
25.	Ethemoglu MS, Kutlu S, Seker FB, et al. Effects of agomelatine on electrocorticogram activity on penicillin-induced seizure model of rats. Neurosci Lett, 2019, 690: 120-125.
26.	Azim MS, Agarwal NB, Vohora D. Effects of agomelatine on pentylenetetrazole-induced kindling, kindling-associated oxidative stress, and behavioral despair in mice and modulation of its actions by luzindole and 1-(m-chlorophenyl) piperazine. Epilepsy Behav, 2017, 72: 140-144.
27.	Aguiar CC, Almeida AB, Araujo PV, et al. Anticonvulsant effects of agomelatine in mice. Epilepsy Behav, 2012, 24(3): 324-328.
28.	Gonzalez de la Aleja J, Saiz-Diaz RA, De la Pena P. Relief of intractable posthypoxic myoclonus after administration of agomelatine. Clin Neuropharmacol, 2012, 35(5): 258-259.
29.	Macdonald RL, Barker JL. Pentylenetetrazol and penicillin are selective antagonists of GABA-mediated post-synaptic inhibition in cultured mammalian neurones. Nature, 1977, 267(5613): 720-721.
30.	Tchekalarova J, Atanasova D, Kortenska L, et al. Agomelatine alleviates neuronal loss through BDNF signaling in the post-status epilepticus model induced by kainic acid in rat. Brain Res Bull, 2019, 147: 22-35.
31.	Gressens P, Schwendimann L, Husson I, et al. Agomelatine, a melatonin receptor agonist with 5-HT(2C) receptor antagonist properties, protects the developing murine white matter against excitotoxicity. Eur J Pharmacol, 2008, 588(1): 58-63.
32.	Klein P, Dingledine R, Aronica E, et al. Commonalities in epileptogenic processes from different acute brain insults: do they translate? Epilepsia, 2018, 59(1): 37-66.
33.	van Vliet EA, Aronica E, Vezzani A, et al. Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies. Neuropathol Appl Neurobiol, 2018, 44(1): 91-111.
34.	Banasr M, Soumier A, Hery M, et al. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry, 2006, 59(11): 1087-1096.
35.	Cardinali DP, Pagano ES, Scacchi Bernasconi PA, et al. Melatonin and mitochondrial dysfunction in the central nervous system. Horm Behav, 2013, 63(2): 322-330.
36.	Rebai R, Jasmin L, Boudah A. Agomelatine effects on fat-enriched diet induced neuroinflammation and depression-like behavior in rats. Biomed Pharmacother, 2021, 135: 111246.
37.	Mohseni-Moghaddam P, Roghani M, Khaleghzadeh-Ahangar H, et al. A literature overview on epilepsy and inflammasome activation. Brain Res Bull, 2021, 172: 229-235.
38.	Kothare SV, Kaleyias J. Sleep and epilepsy in children and adolescents. Sleep Med, 2010, 11(7): 674-685.
39.	Gibbon FM, Maccormac E, Gringras P. Sleep and epilepsy: unfortunate bedfellows. Arch Dis Child, 2019, 104(2): 189-192.
40.	Wichniak A, Wierzbicka A. The effects of antidepressants on sleep in depressed patients with particular reference to trazodone in comparison to agomelatine, amitriptyline, doxepin, mianserine and mirtazapine. Pol Merkur Lekarski, 2011, 31(181): 65-70.
41.	Norman TR, Olver JS. Agomelatine for depression: expanding the horizons? Expert Opin Pharmacother, 2019, 20(6): 647-656.
42.	Tchekalarova J, Kortenska L, Ivanova N, et al. Agomelatine treatment corrects impaired sleep-wake cycle and sleep architecture and increases MT1 receptor as well as BDNF expression in the hippocampus during the subjective light phase of rats exposed to chronic constant light. Psychopharmacology (Berl), 2020, 237(2): 503-518.
43.	Porteous M, Fogel S, Ray L, et al. Increased spindle density correlates with sleep continuity improvements following an eight-week course of a melatonin agonist in people with depression: a proof-of-concept study with agomelatine. Eur J Neurosci, 2021, 54(3): 5112-5119.
44.	Yardimci A, Ozdede MR, Kelestimur H. Agomelatine, a potential multi-target treatment alternative for insomnia, depression, and osteoporosis in postmenopausal women: a hypothetical model. Front Psychiatry, 2021, 12: 654616.
45.	Ballester P, Martinez MJ, Inda MD, et al. Evaluation of agomelatine for the treatment of sleep problems in adults with autism spectrum disorder and co-morbid intellectual disability. J Psychopharmacol, 2019, 33(11): 1395-1406.
46.	Mi WF, Tabarak S, Wang L, et al. Effects of agomelatine and mirtazapine on sleep disturbances in major depressive disorder: evidence from polysomnographic and resting-state functional connectivity analyses. Sleep, 2020, 43(11): 728-735.
47.	Waliszewska-Prosol M, Nowakowska-Kotas M, Chojdak-Lukasiewicz J, et al. Migraine and sleep-an unexplained association? Int J Mol Sci, 2021, 22(11): 621-628.
48.	Peres MF, Masruha MR, Zukerman E, et al. Potential therapeutic use of melatonin in migraine and other headache disorders. Expert Opin Investig Drugs, 2006, 15(4): 367-375.
49.	Fornaro M, Prestia D, Colicchio S, et al. A systematic, updated review on the antidepressant agomelatine focusing on its melatonergic modulation. Curr Neuropharmacol, 2010, 8(3): 287-304.
50.	Fornaro M, Bandini F, Cestari L, et al. Electroretinographic modifications induced by agomelatine: a novel avenue to the understanding of the claimed antidepressant effect of the drug? Neuropsychiatr Dis Treat, 2014, 10: 907-914.
51.	Millan MJ. Multi-target strategies for the improved treatment of depressive states: conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther, 2006, 110(2): 135-370.
52.	Delagrange P, Boutin JA. Therapeutic potential of melatonin ligands. Chronobiol Int, 2006, 23(1-2): 413-418.
53.	Plasencia-Garcia BO, Romero-Guillena SL, Quiros-Lopez A, et al. Agomelatine and migraine management: a successfully treated case series. Ther Adv Psychopharmacol, 2015, 5(4): 243-245.
54.	Naguy A, Alamiri B. Successful agomelatine monotherapy for an adolescent with attention deficit hyperactivity disorder and comorbid migraine. CNS Spectr, 2022, 27(2): 134-135.
55.	Guglielmo R, Martinotti G, Di Giannantonio M, et al. A possible new option for migraine management: agomelatine. Clin Neuropharmacol, 2013, 36(2): 65-67.
56.	Tabeeva GR, Sergeev AV, Gromova SA. Possibilities of preventive treatment of migraine with the MT1- and MT2 agonist and 5-HT2small es, Cyrillic receptor antagonist agomelatin (valdoxan). Zh Nevrol Psikhiatr Im SS Korsakova, 2011, 111(9): 32-36.

1. Zhu L, Chen L, Xu P, et al. Genetic and molecular basis of epilepsy-related cognitive dysfunction. Epilepsy Behav, 2020, 104(Pt A): 106848.
2. Gotra P, Bhardwaj N, Ludhiadch A, et al. Epilepsy and migraine shared genetic and molecular mechanisms: focus on therapeutic strategies. Mol Neurobiol, 2021, 58(8): 3874-3883.
3. Mantegazza M, Cestele S. Pathophysiological mechanisms of migraine and epilepsy: similarities and differences. Neurosci Lett, 2018, 667: 92-102.
4. Terrone G, Balosso S, Pauletti A, et al. Inflammation and reactive oxygen species as disease modifiers in epilepsy. Neuropharmacology, 2020, 167: 107742.
5. Chumboatong W, Khamchai S, Tocharus C, et al. Agomelatine exerts an anti-inflammatory effect by inhibiting microglial activation through TLR4/NLRP3 pathway in pMCAO rats. Neurotox Res, 2022, 40(1): 259-266.
6. Alcocer-Gomez E, Casas-Barquero N, Williams MR, et al. Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in major depressive disorder. Pharmacol Res, 2017, 121: 114-121.
7. Long R, Zhu Y, Zhou S. Therapeutic role of melatonin in migraine prophylaxis: a systematic review. Medicine (Baltimore), 2019, 98(3): e14099.
8. Dehdashtian E, Hosseinzadeh A, Hemati K, et al. Anti-convulsive effect of thiamine and melatonin combination in mice: involvement of oxidative stress. Cent Nerv Syst Agents Med Chem, 2021, 21(2): 125-129.
9. Hosseinzadeh A, Dehdashtian E, Jafari-Sabet M, et al. The effects of vitamin D3 and melatonin combination on pentylenetetrazole-induced seizures in mice. Cent Nerv Syst Agents Med Chem, 2022, [Epub ahead of print].
10. Rocha A, de Lima E, Amaral F, et al. Altered MT1 and MT2 melatonin receptors expression in the hippocampus of pilocarpine-induced epileptic rats. Epilepsy Behav, 2017, 71(Pt A): 23-34.
11. Akkaya R, Gumus E, Akkaya B, et al. Wi-Fi decreases melatonin protective effect and increases hippocampal neuronal damage in pentylenetetrazole induced model seizures in rats. Pathophysiology, 2019, 26(3-4): 375-379.
12. Wan L, Yang G, Sun Y, et al. Combined melatonin and adrenocorticotropic hormone treatment attenuates N-methyl-d-aspartate-induced infantile spasms in a rat model by regulating activation of the HPA axis. Neurosci Lett, 2021, 748: 135713.
13. Peled N, Shorer Z, Peled E, et al. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia, 2001, 42(9): 1208-1210.
14. Verma N, Maiti R, Mishra BR, et al. Effect of add-on melatonin on seizure outcome, neuronal damage, oxidative stress, and quality of life in generalized epilepsy with generalized onset motor seizures in adults: a randomized controlled trial. J Neurosci Res, 2021, 99(6): 1618-1631.
15. Yalyn O, Arman F, Erdogan F, et al. A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures. Epilepsy Behav, 2006, 8(3): 542-526.
16. Yahyavi-Firouz-Abadi N, Tahsili-Fahadan P, Riazi K, et al. Involvement of nitric oxide pathway in the acute anticonvulsant effect of melatonin in mice. Epilepsy Res, 2006, 68(2): 103-113.
17. Albertson TE, Peterson SL, Stark LG, et al. The anticonvulsant properties of melatonin on kindled seizures in rats. Neuropharmacology, 1981, 20(1): 61-66.
18. Moezi L, Shafaroodi H, Hojati A, et al. The interaction of melatonin and agmatine on pentylenetetrazole-induced seizure threshold in mice. Epilepsy Behav, 2011, 22(2): 200-206.
19. Banach M, Gurdziel E, Jedrych M, et al. Melatonin in experimental seizures and epilepsy. Pharmacol Rep, 2011, 63(1): 1-11.
20. Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, et al. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol, 2012, 351(2): 152-166.
21. Krishnakumar A, Nandhu MS, Paulose CS. Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri. Epilepsy Behav, 2009, 16(2): 225-230.
22. Silenieks LB, Carroll NK, Van Niekerk A, et al. Evaluation of selective 5-HT2C agonists in acute seizure models. ACS Chem Neurosci, 2019, 10(7): 3284-3295.
23. Victor Petersen A, Perrier JF. Serotonin prevents temporal lobe epilepsy by inhibiting bursting neurons from the subiculum. Med Sci (Paris), 2017, 33(8-9): 727-729.
24. Demirel EA, Erdogan MA, Cinar BP, et al. The reducing effect of agomelatine on pentylenetetrazol-induced convulsions. Biol Futur, 2019, 70(4): 336-340.
25. Ethemoglu MS, Kutlu S, Seker FB, et al. Effects of agomelatine on electrocorticogram activity on penicillin-induced seizure model of rats. Neurosci Lett, 2019, 690: 120-125.
26. Azim MS, Agarwal NB, Vohora D. Effects of agomelatine on pentylenetetrazole-induced kindling, kindling-associated oxidative stress, and behavioral despair in mice and modulation of its actions by luzindole and 1-(m-chlorophenyl) piperazine. Epilepsy Behav, 2017, 72: 140-144.
27. Aguiar CC, Almeida AB, Araujo PV, et al. Anticonvulsant effects of agomelatine in mice. Epilepsy Behav, 2012, 24(3): 324-328.
28. Gonzalez de la Aleja J, Saiz-Diaz RA, De la Pena P. Relief of intractable posthypoxic myoclonus after administration of agomelatine. Clin Neuropharmacol, 2012, 35(5): 258-259.
29. Macdonald RL, Barker JL. Pentylenetetrazol and penicillin are selective antagonists of GABA-mediated post-synaptic inhibition in cultured mammalian neurones. Nature, 1977, 267(5613): 720-721.
30. Tchekalarova J, Atanasova D, Kortenska L, et al. Agomelatine alleviates neuronal loss through BDNF signaling in the post-status epilepticus model induced by kainic acid in rat. Brain Res Bull, 2019, 147: 22-35.
31. Gressens P, Schwendimann L, Husson I, et al. Agomelatine, a melatonin receptor agonist with 5-HT(2C) receptor antagonist properties, protects the developing murine white matter against excitotoxicity. Eur J Pharmacol, 2008, 588(1): 58-63.
32. Klein P, Dingledine R, Aronica E, et al. Commonalities in epileptogenic processes from different acute brain insults: do they translate? Epilepsia, 2018, 59(1): 37-66.
33. van Vliet EA, Aronica E, Vezzani A, et al. Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies. Neuropathol Appl Neurobiol, 2018, 44(1): 91-111.
34. Banasr M, Soumier A, Hery M, et al. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry, 2006, 59(11): 1087-1096.
35. Cardinali DP, Pagano ES, Scacchi Bernasconi PA, et al. Melatonin and mitochondrial dysfunction in the central nervous system. Horm Behav, 2013, 63(2): 322-330.
36. Rebai R, Jasmin L, Boudah A. Agomelatine effects on fat-enriched diet induced neuroinflammation and depression-like behavior in rats. Biomed Pharmacother, 2021, 135: 111246.
37. Mohseni-Moghaddam P, Roghani M, Khaleghzadeh-Ahangar H, et al. A literature overview on epilepsy and inflammasome activation. Brain Res Bull, 2021, 172: 229-235.
38. Kothare SV, Kaleyias J. Sleep and epilepsy in children and adolescents. Sleep Med, 2010, 11(7): 674-685.
39. Gibbon FM, Maccormac E, Gringras P. Sleep and epilepsy: unfortunate bedfellows. Arch Dis Child, 2019, 104(2): 189-192.
40. Wichniak A, Wierzbicka A. The effects of antidepressants on sleep in depressed patients with particular reference to trazodone in comparison to agomelatine, amitriptyline, doxepin, mianserine and mirtazapine. Pol Merkur Lekarski, 2011, 31(181): 65-70.
41. Norman TR, Olver JS. Agomelatine for depression: expanding the horizons? Expert Opin Pharmacother, 2019, 20(6): 647-656.
42. Tchekalarova J, Kortenska L, Ivanova N, et al. Agomelatine treatment corrects impaired sleep-wake cycle and sleep architecture and increases MT1 receptor as well as BDNF expression in the hippocampus during the subjective light phase of rats exposed to chronic constant light. Psychopharmacology (Berl), 2020, 237(2): 503-518.
43. Porteous M, Fogel S, Ray L, et al. Increased spindle density correlates with sleep continuity improvements following an eight-week course of a melatonin agonist in people with depression: a proof-of-concept study with agomelatine. Eur J Neurosci, 2021, 54(3): 5112-5119.
44. Yardimci A, Ozdede MR, Kelestimur H. Agomelatine, a potential multi-target treatment alternative for insomnia, depression, and osteoporosis in postmenopausal women: a hypothetical model. Front Psychiatry, 2021, 12: 654616.
45. Ballester P, Martinez MJ, Inda MD, et al. Evaluation of agomelatine for the treatment of sleep problems in adults with autism spectrum disorder and co-morbid intellectual disability. J Psychopharmacol, 2019, 33(11): 1395-1406.
46. Mi WF, Tabarak S, Wang L, et al. Effects of agomelatine and mirtazapine on sleep disturbances in major depressive disorder: evidence from polysomnographic and resting-state functional connectivity analyses. Sleep, 2020, 43(11): 728-735.
47. Waliszewska-Prosol M, Nowakowska-Kotas M, Chojdak-Lukasiewicz J, et al. Migraine and sleep-an unexplained association? Int J Mol Sci, 2021, 22(11): 621-628.
48. Peres MF, Masruha MR, Zukerman E, et al. Potential therapeutic use of melatonin in migraine and other headache disorders. Expert Opin Investig Drugs, 2006, 15(4): 367-375.
49. Fornaro M, Prestia D, Colicchio S, et al. A systematic, updated review on the antidepressant agomelatine focusing on its melatonergic modulation. Curr Neuropharmacol, 2010, 8(3): 287-304.
50. Fornaro M, Bandini F, Cestari L, et al. Electroretinographic modifications induced by agomelatine: a novel avenue to the understanding of the claimed antidepressant effect of the drug? Neuropsychiatr Dis Treat, 2014, 10: 907-914.
51. Millan MJ. Multi-target strategies for the improved treatment of depressive states: conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther, 2006, 110(2): 135-370.
52. Delagrange P, Boutin JA. Therapeutic potential of melatonin ligands. Chronobiol Int, 2006, 23(1-2): 413-418.
53. Plasencia-Garcia BO, Romero-Guillena SL, Quiros-Lopez A, et al. Agomelatine and migraine management: a successfully treated case series. Ther Adv Psychopharmacol, 2015, 5(4): 243-245.
54. Naguy A, Alamiri B. Successful agomelatine monotherapy for an adolescent with attention deficit hyperactivity disorder and comorbid migraine. CNS Spectr, 2022, 27(2): 134-135.
55. Guglielmo R, Martinotti G, Di Giannantonio M, et al. A possible new option for migraine management: agomelatine. Clin Neuropharmacol, 2013, 36(2): 65-67.
56. Tabeeva GR, Sergeev AV, Gromova SA. Possibilities of preventive treatment of migraine with the MT1- and MT2 agonist and 5-HT2small es, Cyrillic receptor antagonist agomelatin (valdoxan). Zh Nevrol Psikhiatr Im SS Korsakova, 2011, 111(9): 32-36.

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阿戈美拉汀對癲癇共病偏頭痛患者的治療潛力

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