2. Laufer S, Tries S, Augustin J, Dannhardt G. Pharmacological profile of a new pyrrolizine derivative inhibiting the enzymes cyclo-oxygenase and 5-lipoxygenase. Arzneimittelforschung. 1994;44:629–36.
3. Laufer S, Tries S, Augustin J, et al. Acute and chronic anti-inflammatory properties of [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2, 3-dihydro-1H-pyrrolizine-5-yl]-acetic acid. Arzneimittelforschung. 1995;45:27–32.
4. Laufer S, Tries S, Augustin J, et al. Gastrointestinal tolerance of [2,2-dimethyl-6-(4-chlorophenyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid in the rat. Arzneimittelforschung. 1994;44:1329–33.
5. Alvaro-Gracia JM. Licofelone--clinical update on a novel LOX/COX inhibitor for the treatment of osteoarthritis. Rheumatology (Oxford). 2004;43:Suppl 1. i21–5.
6. Koeberle A, Werz O. Microsomal prostaglandin E2 synthase-1. Levin JI, Laufer S, editors. Anti-Inflammatory Drug Discovery. 1st ed. London: Royal Society of Chemistry; 2012. p. 7–34.
7. Raynauld JP, Martel-Pelletier J, Bias P, et al. Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann Rheum Dis. 2009;68:938–47.
8. Tries S, Laufer S. The pharmacological profile of ML3000: a new pyrrolizine derivative inhibiting the enzymes cyclo-oxygenase and 5-lipoxygenase. Inflammopharmacology. 2001;9:113–24.
9. Tries S, Neupert W, Laufer S. The mechanism of action of the new antiinflammatory compound ML3000: inhibition of 5-LOX and COX-1/2. Inflamm Res. 2002;51:135–43.
10. Wallace JL, Carter L, McKnight W, Tries S, Laufer S. ML 3000 reduces gastric prostaglandin synthesis without causing mucosal injury. Eur J Pharmacol. 1994;271:525–31.
11. Auriel E, Regev K, Korczyn AD. Nonsteroidal anti-inflammatory drugs exposure and the central nervous system. Handb Clin Neurol. 2014;119:577–84.
12. Bishnoi M, Patii CS, Kumar A, Kulkarni SK. Relative role of cyclooxygenase-2 (COX-2) inhibitors and lipoxygenase (LOX) inhibitors in aging induced dementia and oxidative damage. Ann Neurosci. 2010;12:6–11.
14. Kalonia H, Kumar P, Kumar A. Licofelone attenuates quinolinic acid induced Huntington like symptoms: possible behavioral, biochemical and cellular alterations. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:607–15.
15. Kumar A, Sharma S, Prashar A, Deshmukh R. Effect of licofelone--a dual COX/5-LOX inhibitor in intracerebroventricular streptozotocin-induced behavioral and biochemical abnormalities in rats. J Mol Neurosci. 2015;55:749–59.
16. Mousavi SE, Saberi P, Ghasemkhani N, Fakhraei N, Mokhtari R, Dehpour AR. Licofelone attenuates LPS-induced depressive-like behavior in mice: a possible role for nitric oxide. J Pharm Pharm Sci. 2018;21:184–94.
17. Eslami SM, Moradi MM, Ghasemi M, Dehpour AR. Anticonvulsive effects of licofelone on status epilepticus induced by lithium-pilocarpine in wistar rats: a role for inducible nitric Oxide synthase. J Epilepsy Res. 2016;6:51–8.
18. Payandemehr B, Khoshneviszadeh M, Varastehmoradi B, et al. A COX/5-LOX inhibitor licofelone revealed anticonvulsant properties through iNOS diminution in mice. Neurochem Res. 2015;40:1819–28.
19. Baran H, Vass K, Lassmann H, Hornykiewicz O. The cyclooxygenase and lipoxygenase inhibitor BW755C protects rats against kainic acid-induced seizures and neurotoxicity. Brain Res. 1994;646:201–6.
20. Dhir A. An update of cyclooxygenase (COX)-inhibitors in epilepsy disorders. Expert Opin Investig Drugs. 2019;28:191–205.
21. Ghasemi M, Schachter SC. The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav. 2011;22:617–40.
22. McNamara JO, Russell RD, Rigsbee L, Bonhaus DW. Anticonvulsant and antiepileptogenic actions of MK-801 in the kindling and electroshock models. Neuropharmacology. 1988;27:563–8.
23. Mintz M, Rose IC, Herberg LJ. The effect of the NMDA receptor antagonist, MK-801, on the course and outcome of kindling. Pharmacol Biochem Behav. 1990;35:815–21.
24. O'Neill SK, Bolger GT. Anticonvulsant activity of MK-801 and nimodipine alone and in combination against pentylenetetrazole and strychnine. Pharmacol Biochem Behav. 1989;32:595–600.
25. Tricklebank MD, Singh L, Oles RJ, Preston C, Iversen SD. The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. Eur J Pharmacol. 1989;167:127–35.
26. Ormandy GC, Jope RS, Snead OC. Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats. Exp Neurol. 1989;106:172–80.
27. Walton NY, Treiman DM. Motor and electroencephalographic response of refractory experimental status epilepticus in rats to treatment with MK-801, diazepam, or MK-801 plus diazepam. Brain Res. 1991;553:97–104.
28. Clineschmidt BV, Martin GE, Bunting PR. Anticonvulsant activity of (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev Res. 1982;2:123–34.
29. Sparenborg S, Brennecke LH, Jaax NK, Braitman DJ. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by soman. Neuropharmacology. 1992;31:357–68.
30. Berg M, Bruhn T, Johansen FF, Diemer NH. Kainic acid-induced seizures and brain damage in the rat: different effects of NMDA- and AMPA receptor antagonists. Pharmacol Toxicol. 1993;73:262–8.
31. Fariello RG, Golden GT, Smith GG, Reyes PF. Potentiation of kainic acid epileptogenicity and sparing from neuronal damage by an NMDA receptor antagonist. Epilepsy Res. 1989;3:206–13.
32. Lees GJ. Effects of anaesthetics, anticonvulsants and glutamate antagonists on kainic acid-induced local and distal neuronal loss. J Neurol Sci. 1992;108:221–8.
33. Ghasemi M, Claunch J, Niu K. Pathologic role of nitrergic neurotransmission in mood disorders. Prog Neurobiol. 2019;173:54–87.
34. Ghasemi M, Fatemi A. Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases. Neurosci Biobehav Rev. 2014;45:168–82.
35. Faghir-Ghanesefat H, Keshavarz-Bahaghighat H, Rajai N, et al. The possible role of nitric oxide pathway in pentylenetetrazole preconditioning against seizure in mice. J Mol Neurosci. 2019;67:477–83.
36. Ghasemi M, Shafaroodi H, Nazarbeiki S, et al. Inhibition of NMDA receptor/ NO signaling blocked tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice. Epilepsy Res. 2010;91:39–48.
37. Ghasemi M, Shafaroodi H, Nazarbeiki S, et al. Voltage-dependent calcium channel and NMDA receptor antagonists augment anticonvulsant effects of lithium chloride on pentylenetetrazole-induced clonic seizures in mice. Epilepsy Behav. 2010;18:171–8.
38. Gholipour T, Ghasemi M, Riazi K, Ghaffarpour M, Dehpour AR. Seizure susceptibility alteration through 5-HT(3) receptor: modulation by nitric oxide. Seizure. 2010;19:17–22.
39. Panigrahi S, Li DD, Surai S, Ghosh A, Hong H. 5-lipoxygenase: emerging therapeutic targets in central nervous system disorders. Int J Adv Res Biol Sci. 2018;5:20–9.
40. Homayoun H, Khavandgar S, Dehpour AR. The involvement of endogenous opioids and nitricoxidergic pathway in the anticonvulsant effects of foot-shock stress in mice. Epilepsy Res. 2002;49:131–42.
41. Payandemehr B, Rahimian R, Bahremand A, et al. Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine. Physiol Behav. 2013;118:52–7.
42. Löscher W. Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy Res. 2002;50:105–23.
43. Kulkarni S, Singh VP. Licofelone-A novel analgesic and anti-inflammatory agent. Curr Top Med Chem. 2007;7:251–63.
44. Phillis JW, Horrocks LA, Farooqui AA. Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders. Brain Res Rev. 2006;52:201–43.
45. Dhir A, Naidu PS, Kulkarni SK. Effect of cyclooxygenase inhibitors on pentylenetetrazol (PTZ)-induced convulsions: possible mechanism of action. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1478–85.
46. Sokola BS. Dual LOX/COX inhibition: a novel strategy to prevent neurovascular leakage in epilepsy [master’s thesis]. [Lexington (KY)]: University of Kentucky; 2018.
47. Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. 1993;11:371–86.
49. Roch C, Leroy C, Nehlig A, Namer IJ. Magnetic resonance imaging in the study of the lithium-pilocarpine model of temporal lobe epilepsy in adult rats. Epilepsia. 2002;43:325–35.
51. Tomkins O, Shelef I, Kaizerman I, et al. Blood-brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry. 2008;79:774–7.
52. van Vliet EA, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, Gorter JA. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain. 2007;130:Pt 2. 521–34.
53. Collard CD, Park KA, Montalto MC, et al. Neutrophil-derived glutamate regulates vascular endothelial barrier function. J Biol Chem. 2002;277:14801–11.
54. Koenig H, Trout JJ, Goldstone AD, Lu CY. Capillary NMDA receptors regulate blood-brain barrier function and breakdown. Brain Res. 1992;588:297–303.
57. Seegers U, Potschka H, Löscher W. Expression of the multidrug transporter P-glycoprotein in brain capillary endothelial cells and brain parenchyma of amygdala-kindled rats. Epilepsia. 2002;43:675–84.
58. van Vliet E, Aronica E, Redeker S, et al. Selective and persistent upregulation of mdr1b mRNA and P-glycoprotein in the parahippocampal cortex of chronic epileptic rats. Epilepsy Res. 2004;60:203–13.
59. Auzmendi JA, Orozco-Suárez S, Bañuelos-Cabrera I, et al. P-glycoprotein contributes to cell membrane depolarization of hippocampus and neocortex in a model of repetitive seizures induced by pentylenetetrazole in rats. Curr Pharm Des. 2013;19:6732–8.
60. Bauer B, Hartz AM, Pekcec A, Toellner K, Miller DS, Potschka H. Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier through glutamate and cyclooxygenase-2 signaling. Mol Pharmacol. 2008;73:1444–53.
61. Zibell G, Unkrüer B, Pekcec A, et al. Prevention of seizure-induced up-regulation of endothelial P-glycoprotein by COX-2 inhibition. Neuropharmacology. 2009;56:849–55.
62. Zeng H, Liu X, Dou S, et al. Huang-Lian-Jie-Du-Tang exerts anti-inflammatory effects in rats through inhibition of nitric oxide production and eicosanoid biosynthesis via the lipoxygenase pathway. J Pharm Pharmacol. 2009;61:1699–707.
63. Kalia LV, Kalia SK, Salter MW. NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol. 2008;7:742–55.
64. Rothman SM, Olney JW. Excitotoxity and the NMDA receptor. Trends Neurosci. 1987;10:299–302.
65. Waxman EA, Lynch DR. N-methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease. Neuroscientist. 2005;11:37–49.
66. Ahmed MM, Arif M, Chikuma T, Kato T. Pentylenetetrazol-induced seizures affect the levels of prolyl oligopeptidase, thimet oligopeptidase and glial proteins in rat brain regions, and attenuation by MK-801 pretreatment. Neurochem Int. 2005;47:248–59.
67. Croucher MJ, Collins JF, Meldrum BS. Anticonvulsant action of excitatory amino acid antagonists. Science. 1988;216:899–901.
68. Gmiro V, Serdyuk S. Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia. Bull Exp Biol Med. 2008;145:728–30.
69. Mareš P, Mikulecká A. Different effects of two N-methyl-D-aspartate receptor antagonists on seizures, spontaneous behavior, and motor performance in immature rats. Epilepsy Behav. 2009;14:32–9.
70. Velíšek L, Velíšková J, Ptachewich Y, Shinnar S, Moshé SL. Effects of MK-801 and phenytoin on flurothyl-induced seizures during development. Epilepsia. 1995;36:179–85.
71. Krystal AD, Weiner RD, Dean MD, et al. Comparison of seizure duration, ictal EEG, and cognitive effects of ketamine and methohexital anesthesia with ECT. J Neuropsychiatry Clin Neurosci. 2003;15:27–34.
72. Faught E, Sachdeo RC, Remler MP, et al. Felbamate monotherapy for partial-onset seizures: an active-control trial. Neurology. 1993;43:688–92.
73. Shi LL, Dong J, Ni H, Geng J, Wu T. Felbamate as an add-on therapy for refractory partial epilepsy. Cochrane Database Syst Rev. 2017;7:CD008295