The role of opioid and nitrergic systems in dual modulation of seizure susceptibility

Muhammad Imran Khan, Farid Ullah Shah, Abdul Wahab, Vahid Nikoui, Ahmad Reza Dehpour


Epilepsy is a chronic disorder presented by recurrent episodes of seizures and affect worldwide individuals.  The underlying mechanism of seizure is still elusive. Hence, there is still a need to determine the contribution of various systems in neurobiology and treatment of seizure. Evidence shows that opioid and nitrergic systems within the brain interact to modulate various physiological and pathological conditions including memory, pain, reward, addiction, depression, and seizure. Various studies revealed that diverse dose of opioids such as morphine has dual modulation in seizure susceptibility. For instance, it is reported that morphine at lower doses (0.5, 1, and 3 mg/kg) exerts an anticonvulsant effect in experimental seizure models, whereas at higher doses (15, 30, and 60 mg/kg) it could exacerbate the seizure. Similarly, nitrergic system has also been observed to possess dual effects in modulating the seizure threshold. Therefore, understanding of opioidergic and nitrergic systems interaction in seizure seems important to achieve the successful goal of seizure management. This review aimed to clarify and provide insight into how opioidergic and nitrergic systems interact in brain and mediate seizure behavior.

Keywords: Opioids; Nitric oxide; Seizures; Morphine 

Full Text:



Honar H, Riazi K, Homayoun H, Demehri S, Dehghani M, et al. Lithium inhibits the modulatory effects of morphine on susceptibility to pentylenetetrazole-induced clonic seizure in mice: involvement of a nitric oxide pathway. Brain research, (2004); 1029(1): 48-55.

Shafaroodi H, Samini M, Moezi L, Homayoun H, Sadeghipour H, et al. The interaction of cannabinoids and opioids on pentylenetetrazole-induced seizure threshold in mice. Neuropharmacology, (2004); 47(3): 390-400.

Homayoun H, Sayyah M, Dehpour AR. The additive effect of opioids and nitric oxide in increasing pentylenetetrazole‐induced seizure threshold in cholestatic mice. Journal of gastroenterology and hepatology, (2002); 17(1): 96-101.

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 research, (2002); 49(2): 131-142.

Honar H, Riazi K, Homayoun H, Sadeghipour H, Rashidi N, et al. Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures. Neuroscience, (2004); 129(3): 733-742.

Homayoun H, Khavandgar S, Namiranian K, Gaskari SA, Dehpour AR. The role of nitric oxide in anticonvulsant and proconvulsant effects of morphine in mice. Epilepsy research, (2002); 48(1-2): 33-41.

Ghasemi M, Shafaroodi H, Nazarbeiki S, Meskar H, Ghasemi A, et al. Inhibition of NMDA receptor/NO signaling blocked tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice. Epilepsy research, (2010); 91(1): 39-48.

Khavandgar S, Homayoun H, Dehpour AR. The role of nitric oxide in the proconvulsant effect of δ-opioid agonist SNC80 in mice. Neuroscience letters, (2002); 329(2): 237-239.

Khavandgar S, Homayoun H, Dehpour AR. Mediation of nitric oxide in inhibitory effect of morphine against electroshock-induced convulsions in mice. Pharmacology Biochemistry and Behavior, (2003); 74(4): 795-801.

Gholipour T, Riazi K, Noorian AR, Jannati A, Honar H, et al. Seizure susceptibility alteration following reversible cholestasis in mice: modulation by opioids and nitric oxide. European journal of pharmacology, (2008); 580(3): 322-328.

Potschka H, Friderichs E, Löscher W. Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. British journal of pharmacology, (2000); 131(2): 203-212.

Ceyhan M, Kayir H, Uzbay IT. Investigation of the effects of tianeptine and fluoxetine on pentylenetetrazole-induced seizures in rats. Journal of psychiatric research, (2005); 39(2): 191-196.

Stögmann E, Zimprich A, Baumgartner C, Aull‐Watschinger S, Höllt V, et al. A functional polymorphism in the prodynorphin gene promotor is associated with temporal lobe epilepsy. Annals of neurology, (2002); 51(2): 260-263.

Montaser-Kouhsari L, Payandemehr B, Gholipour T, Ziai P, Nabavizadeh P, et al. A role for opioid system in the proconvulsant effects of sildenafil on the pentylenetetrazole-induced clonic seizure in mice. Seizure, (2011); 20(5): 409-413.

Banks ML, Roma PG, Folk JE, Rice KC, Negus SS. Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis. Psychopharmacology, (2011); 216(3): 431-439.

Rubaj A, Gustaw K, Zgodziński W, Kleinrok Z, Sieklucka-Dziuba M. The role of opioid receptors in hypoxic preconditioning against seizures in brain. Pharmacology Biochemistry and Behavior, (2000); 67(1): 65-70.

Hammers A, Asselin M-C, Hinz R, Kitchen I, Brooks DJ, et al. Upregulation of opioid receptor binding following spontaneous epileptic seizures. Brain, (2007); 130(4): 1009-1016.

Schwarzer C. 30 years of dynorphins—new insights on their functions in neuropsychiatric diseases. Pharmacology & therapeutics, (2009); 123(3): 353-370.

Madar I, Lesser RP, Krauss G, Zubieta JK, Lever JR, et al. Imaging of δ‐and μ‐opioid receptors in temporal lobe epilepsy by positron emission tomography. Annals of neurology, (1997); 41(3): 358-367.

Saboory E, Derchansky M, Ismaili M, Jahromi SS, Brull R, et al. Mechanisms of morphine enhancement of spontaneous seizure activity. Anesthesia & Analgesia, (2007); 105(6): 1729-1735.

Agrawal N, Alonso A, Ragsdale DS. Increased persistent sodium currents in rat entorhinal cortex layer V neurons in a post–status epilepticus model of temporal lobe epilepsy. Epilepsia, (2003); 44(12): 1601-1604.

Zhao P, Ma M-C, Qian H, Xia Y. Down-regulation of delta-opioid receptors in Na+H<+ exchanger 1 null mutant mouse brain with epilepsy. Neuroscience research, (2005); 53(4): 442-446.

Riazi K, Honar H, Homayoun H, Rashidi N, Kiani S, et al. The synergistic anticonvulsant effect of agmatine and morphine: possible role of alpha 2-adrenoceptors. Epilepsy research, (2005); 65(1): 33-40.

Sayyah M, Javad-Pour M, Ghazi-Khansari M. The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in mice: involvement of proinflammatory factors: nitric oxide and prostaglandins. Neuroscience, (2003); 122(4): 1073-1080.

Krueger HM, Eddy NB, Sumwalt M The pharmacology of the opium alkaloids. (1941); (vol 2), Chapter 1,. publication; US Government Printing Office.

Karadag C, Dokmeci D, Dost T, Ulugol A, Dokmeci I. Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice. Brazilian Journal of Medical and Biological Research, (2000); 33(3): 327-330.

Frenk H. Pro-and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems. Brain Research Reviews, (1983); 6(2): 197-210.

Tortella FC, Cowan A, Adler MW. Comparison of the anticonvulsant effects of opioid peptides and etorphine in rats after icv administration. Life sciences, (1981); 29(10): 1039-1045.

Bajorek J, Lomax P. Modulation of spontaneous seizures in the Mongolian gerbil: Effects of β-endorphin. Peptides, (1982); 3(1): 83-86.

Mannino RA, Wolf HH. Opiate receptor phenomenon: proconvulsant action of morphine in the mouse. Life sciences, (1974); 15(12): 2089-2096.

Urca G, Frenk H. Pro-and anticonvulsant action of morphine in rats. Pharmacology Biochemistry and Behavior, (1980); 13(3): 343-347.

Corrado AP, Longo V. An electrophysiological analysis of the convulsant action of morphine, codeine and thebaine. Archives internationales de pharmacodynamie et de thérapie, ( 1961);132:255-269

Tatum A, Seevers M, Collins K. Morphine addiction and its physiological interpretation based on experimental evidences. Journal of Pharmacology and Experimental Therapeutics, (1929); 36(3): 447-475.

Urca G, Frenk H, Liebeskind JC, Taylor AN. Morphine and enkephalin: analgesic and epileptic properties. Science, (1977); 197(4298): 83-86.

Khan MI, Shirzadian A, Haj-Mirzaian A, Mehr SE, Dehpour AR, et al. Proconvulsant effect of post-weaning social isolation stress may be associated with dysregulation of opioid system in the male mice. Medical hypotheses, (2015); 84(5): 445-447.

Shafaroodi H, Asadi S, Sadeghipour H, Ghasemi M, Ebrahimi F, et al. Role of ATP-sensitive potassium channels in the biphasic effects of morphine on pentylenetetrazole-induced seizure threshold in mice. Epilepsy research, (2007); 75(1): 63-69.

Ostadhadi S, Haj‐Mirzaian A, Nikoui V, Kordjazy N, Dehpour AR. Involvement of opioid system in antidepressant‐like effect of the cannabinoid CB1 receptor inverse agonist AM‐251 after physical stress in mice. Clinical and Experimental Pharmacology and Physiology, (2016); 43(2): 203-212.

Hofmann ME, Frazier CJ. Marijuana, endocannabinoids, and epilepsy: potential and challenges for improved therapeutic intervention. Experimental neurology, (2013); 1 (244): 43-50.

Loacker S, Sayyah M, Wittmann W, Herzog H, Schwarzer C. Endogenous dynorphin in epileptogenesis and epilepsy: anticonvulsant net effect via kappa opioid receptors. Brain, (2007); 130(4): 1017-1028.

Jackson HC, Nutt D. Investigation of the involvement of opioid receptors in the action of anticonvulsants. Psychopharmacology, (1993); 111(4): 486-490.

Shafaroodi H, Baradaran N, Moezi L, Dehpour S, Kabiri T, et al. Morphine sensitization in the pentylenetetrazole-induced clonic seizure threshold in mice: Role of nitric oxide and μ receptors. Epilepsy & Behavior, (2011); 20(4): 602-606.

Riazi K, Roshanpour M, Rafiei‐Tabatabaei N, Homayoun H, Ebrahimi F, et al. The proconvulsant effect of sildenafil in mice: role of nitric oxide–cGMP pathway. British journal of pharmacology, (2006); 147(8): 935-943.

Snyder E, Shearer D, Beck E, Dustman R. Naloxone-induced electrographic seizures in the primate. Psychopharmacology, (1980); 67(3): 211-214.

Jóhannesson T, Milthers K. The Lethal Action of Morphine and Nalorphine given jointly to Morphine Tolerant and Non‐Tolerant Rats. Acta pharmacologica et toxicologica, (1963); 20(1): 80-89.

Riazi K, Honar H, Homayoun H, Rashidi N, Dehghani M, et al. Sex and estrus cycle differences in the modulatory effects of morphine on seizure susceptibility in mice. Epilepsia, (2004); 45(9): 1035-1042.

Jang C-G, Lee S-Y, Loh HH, Ho K. Lack of μ-opioid receptor leads to an increase in the NMDA receptor subunit mRNA expression and NMDA-induced convulsion. Molecular brain research, (2001); 94(1): 105-111.

Javadi S, Ejtemaeimehr S, Keyvanfar HR, Moghaddas P, Aminian A, et al. Pioglitazone potentiates development of morphine-dependence in mice: Possible role of NO/cGMP pathway. Brain research, (2013); 151022-37.

Javanmardi K, Parviz M, Keshavarz M, Minaii B, Dehpour AR, et al. Involvement of N‐methyl‐D‐aspartate receptors and nitric oxide in the rostral ventromedial medulla in modulating morphine pain‐inhibitory signals from the periaqueductal grey matter in rats. Clinical and experimental pharmacology and physiology, (2005); 32(7): 585-589.

Dehpour A, Sadeghipour H, Nowroozi A, Akbarloo N. The effect of the serotonergic system on opioid withdrawal‐like syndrome in a mouse model of cholestasis. Human Psychopharmacology: Clinical and Experimental, (2000); 15(6): 423-428.

Haj-Mirzaian A, Ostadhadi S, Kordjazy N, Dehpour AR, Mehr SE. Opioid/NMDA receptors blockade reverses the depressant-like behavior of foot shock stress in the mouse forced swimming test. European journal of pharmacology, (2014); 735, 26-31.

Dehpour AR, Samini M, Arad MA, Namiranian K. Clonidine Attenuates Naloxone‐Induced Opioid‐Withdrawal Syndrome in Cholestatic Mice. Basic & Clinical Pharmacology & Toxicology, (2001); 89(3): 129-132.

Haj-Mirzaian A, Kordjazy N, Ostadhadi S, Amiri S, Haj-Mirzaian A, et al. Fluoxetine reverses the behavioral despair induced by neurogenic stress in mice: role of N-methyl-d-aspartate and opioid receptors. Canadian journal of physiology and pharmacology, (2016); 94(6): 599-612.

Dehpour AR, Meysami F, Ebrahimi‐Daryani N, Akbarloo N. Inhibition by lithium of opioid withdrawal‐like syndrome and physical dependency in a model of acute cholestasis in mice. Human Psychopharmacology: Clinical and Experimental, (1998); 13(6): 407-412.

Homayoun H, Khavandgar S, Dehpour AR. The Role of α2‐Adrenoceptors in the Modulatory Effects of Morphine on Seizure Susceptibility in Mice. Epilepsia, (2002); 43(8): 797-804.

Snyder SH, Bredt DS. Biological roles of nitric oxide. Scientific American, (1992); 266(5): 68-77

Edwards T, Rickard N. New perspectives on the mechanisms through which nitric oxide may affect learning and memory processes. Neuroscience & Biobehavioral Reviews, (2007); 31(3): 413-425.

Ostadhadi S, Ahangari M, Nikoui V, Norouzi-Javidan A, Zolfaghari S, et al. Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test. Biomedicine & Pharmacotherapy, 82; (2016): 713-721.

Amiri S, Haj-Mirzaian A, Momeny M, Amini-Khoei H, Rahimi-Balaei M, et al. Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice. Neuroscience, 340 (2017): 373-383.

Nathan C, Xie Q-w. Nitric oxide synthases: roles, tolls, and controls. Cell, (1994); 78(6): 915-918.

Dehpour A, Akbarloo N, Ghafourifar P. Endogenous nitric oxide modulates naloxone-precipitated withdrawal signs in a mouse model with acute cholestasis. Behavioural pharmacology, (1998); 9(1): 77-80.

Nahavandi A, Mani AR, Homayounfar H, Akbari MR, Dehpour AR. The role of the interaction between endogenous opioids and nitric oxide in the pathophysiology of ethanol‐induced gastric damage in cholestatic rats. Fundamental & clinical pharmacology, (2001); 15(3): 181-187.

Homayoun H, Khavandgar S, Mehr SE, Namiranian K, Dehpour A. The effects of FK506 on the development and expression of morphine tolerance and dependence in mice. Behavioural pharmacology, (2003); 14(2): 121-127.

Javadi-Paydar M, Ghiassy B, Ebadian S, Rahimi N, Norouzi A, et al. Nitric oxide mediates the beneficial effect of chronic naltrexone on cholestasis-induced memory impairment in male rats. Behavioural pharmacology, (2013); 24(3): 195-206.

Namiranian K, Samini M, Mehr SE, Gaskari SA, Rastegar H, et al. Mesenteric vascular bed responsiveness in bile duct-ligated rats: roles of opioid and nitric oxide systems. European journal of pharmacology, (2001); 423(2-3): 185-193.

Gaskari SA, Mani AR, Ejtemaei‐Mehr S, Namiranian K, Homayoun H, et al. Do endogenous opioids contribute to the bradycardia of rats with obstructive cholestasis? Fundamental & clinical pharmacology, (2002); 16(4): 273-279.

Hajrasouliha AR, Tavakoli S, Jabehdar-Maralani P, Shafaroodi H, Borhani AA, et al. Resistance of cholestatic rats against epinephrine-induced arrhythmia: the role of nitric oxide and endogenous opioids. European journal of pharmacology, (2004); 499(3): 307-313.

Ebrahimi F, Tavakoli S, Hajrasouliha AR, Shafaroodi H, Sadeghipour H, et al. Contribution of endogenous opioids and nitric oxide to papillary muscle contractile impairment in cholestatic rats. European journal of pharmacology, (2005); 523(1-3): 93-100.

Ghafourifar P, Dehpour AR, Akbarloo N. Inhibition by L-NA, a nitric oxide synthase inhibitor, of naloxone-precpitated withdrawal signs in a mouse model of cholestasis. Life sciences, (1997); 60(19): PL265-PL270.

Haj-Mirzaian A, Hamzeh N, Javadi-Paydar M, Estakhri MRA, Dehpour AR. Resistance to depression through interference of opioid and nitrergic systems in bile-duct ligated mice. European journal of pharmacology, (2013); 708(1-3): 38-43.

Homayoun H, Khavandgar S, Dehpour AR. The selective role of nitric oxide in opioid-mediated footshock stress antinociception in mice. Physiology & behavior, (2003); 79(4-5): 567-573.

Sadeghipour H, Dehghani M, Dehpour AR. Role of opioid and nitric oxide systems in the nonadrenergic noncholinergic-mediated relaxation of corpus cavernosum in bile duct-ligated rats. European journal of pharmacology, (2003); 460(2-3): 201-207.

Kiani S, Valizadeh B, Hormazdi B, Samadi H, Najafi T, et al. Alteration in male reproductive system in experimental cholestasis: roles for opioids and nitric oxide overproduction. European journal of pharmacology, (2009); 615(1-3): 246-251.

Yahyavi-Firouz-Abadi N, Tahsili-Fahadan P, Riazi K, Ghahremani MH, Dehpour AR. Melatonin enhances the anticonvulsant and proconvulsant effects of morphine in mice: role for nitric oxide signaling pathway. Epilepsy research, (2007); 75(2-3): 138-144.

Ebrahimi F, Tavakoli S, Hajrasouliha AR, Sadeghipour H, Dehghani M, et al. Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β‐adrenergic stimulation in cirrhotic rats. Fundamental & clinical pharmacology, (2006); 20(5): 461-471.

Tavakoli S, Hajrasouliha AR, Jabehdar-Maralani P, Ebrahimi F, Solhpour A, et al. Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: the roles of nitric oxide and endogenous opioid peptides. Journal of hepatology, (2007); 46(3): 432-439.

Demehri S, Samini M, Namiranian K, Rastegar H, Mehr S, et al. Alpha2‐adrenoceptor and NO mediate the opioid subsensitivity in isolated tissues of cholestatic animals. Autonomic and Autacoid Pharmacology, (2003); 23(4): 201-207.

Demehri S, Namiranian K, Mehr SE, Rastegar H, Shariftabrizi A, et al. Alpha-2-adrenoceptor hyporesponsiveness in isolated tissues of cholestatic animals: involvement of opioid and nitric oxide systems. Life sciences, (2003); 73(2): 209-220.

Payandemehr B, Rahimian R, Bahremand A, Ebrahimi A, Saadat S, et al. Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine. Physiology & behavior, (2013); 118: 52-57.

Hassanipour M, Shirzadian A, Boojar MM-A, Abkhoo A, Abkhoo A, et al. Possible involvement of nitrergic and opioidergic systems in the modulatory effect of acute chloroquine treatment on pentylenetetrazol induced convulsions in mice. Brain research bulletin, (2016); 121: 124-130.

Leza J-C, Lizasoain I, San-Martín-Clark O, Lorenzo P. Morphine-induced changes in cerebral and cerebellar nitric oxide synthase activity. European journal of pharmacology, (1995); 285(1): 95-98.

Stefano GB, Hartman A, Bilfinger TV, Magazine HI, Liu Y, et al. Presence of the μ3 opiate receptor in endothelial cells coupling to nitric oxide production and vasodilation. Journal of Biological Chemistry, (1995); 270(51): 30290-30293.

Kampa M, Hatzoglou A, Notas G, Niniraki M, Kouroumalis E, et al. Opioids are non-competitive inhibitors of nitric oxide synthase in T47D human breast cancer cells. Cell death and differentiation, (2001); 8(9): 943.

Barjavel MJ, Bhargava HN. Effect of opioid receptor agonists on nitric oxide synthase activity in rat cerebral cortex homogenate. Neuroscience letters, (1994); 181(1-2): 27-30.

Buisson A, Lakhmeche N, Verrecchia C, Plotkine M, Boulu R. Nitric oxide: an endogenous anticonvulsant substance. Neuroreport, (1993); 4(4): 444-446.

Gholipour T, Ghasemi M, Riazi K, Ghaffarpour M, Dehpour AR. Seizure susceptibility alteration through 5-HT3 receptor: Modulation by nitric oxide. Seizure, (2010); 19(1): 17-22.

Bahremand A, Payandemehr B, Rahimian R, Ziai P, Pourmand N, et al. The role of 5-HT3 receptors in the additive anticonvulsant effects of citalopram and morphine on pentylenetetrazole-induced clonic seizures in mice. Epilepsy & Behavior, (2011); 21(2): 122-127.

Payandemehr B, Bahremand A, Rahimian R, Ziai P, Amouzegar A, et al. 5-HT3 receptor mediates the dose-dependent effects of citalopram on pentylenetetrazole-induced clonic seizure in mice: Involvement of nitric oxide. Epilepsy research, (2012); 101(3): 217-227.

Adabi Mohazab R, Javadi-Paydar M, Delfan B, Dehpour AR. Possible involvement of PPAR-gamma receptor and nitric oxide pathway in the anticonvulsant effect of acute pioglitazone on pentylenetetrazole-induced seizures in mice. Epilepsy research, (2012); 101(1): 28-35.

Amiri S, Shirzadian A, Haj-Mirzaian A, Imran-Khan M, Balaei MR, et al. Involvement of the nitrergic system in the proconvulsant effect of social isolation stress in male mice. Epilepsy & Behavior, (2014); 41: 158-163.

Payandemehr B, Rahimian R, Gooshe M, Bahremand A, Gholizadeh R, et al. Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice. Epilepsy & Behavior, (2014); 34: 99-104.

De Sarro G, Di Paola ED, De Sarro A, Vidal MJ. L-Arginine potentiates excitatory amino acid-induced seizures elicited in the deep prepiriform cortex. European journal of pharmacology, (1993); 230(2): 151-158.

Itzhak Y. Attenuation of cocaine kindling by 7-nitroindazole, an inhibitor of brain nitric oxide synthase. Neuropharmacology, (1996); 35(8): 1065-1073.

Akula KK, Dhir A, Kulkarni S. Nitric oxide signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol-induced seizure threshold in mice. European journal of pharmacology, (2008); 587(1-3): 129-134.

ÜZÜM G, AKGÜN-DAR K, Bahcekapili N, DILER AS, ZIYLAN YZ. Nitric oxide involvement in seizures elicited by pentylentetrazol and sex dependence. International journal of neuroscience, (2005); 115(11): 1502-1514.

Payandemehr B, Khoshneviszadeh M, Varastehmoradi B, Gholizadeh R, Bahremand T, et al. A COX/5-LOX inhibitor licofelone revealed anticonvulsant properties through inos diminution in mice. Neurochemical research, (2015); 40(9): 1819-1828.

Zandieh A, Maleki F, Hajimirzabeigi A, Zandieh B, Khalilzadeh O, et al. Anticonvulsant effect of celecoxib on pentylenetetrazole-induced convulsion: Modulation by NO pathway. Acta neurobiologiae experimentalis, (2010); 70(4): 390-397.

Starr MS, Starr BS. Paradoxical facilitation of pilocarpine-induced seizures in the mouse by MK-801 and the nitric oxide synthesis inhibitor L-NAME. Pharmacology Biochemistry and Behavior, (1993); 45(2): 321-325.

Theard MA, Baughman VL, Wang Q, Pelligrino DA, Albrecht RF. The role of nitric oxide in modulating brain activity and blood flow during seizure. Neuroreport, (1995); 6(6): 921-924.

Ayyildiz M, Yildirim M, Agar E. The involvement of nitric oxide in the anticonvulsant effects of α-tocopherol on penicillin-induced epileptiform activity in rats. Epilepsy research, (2007); 73(2): 166-172.

Bahremand A, Nasrabady SE, Shafaroodi H, Ghasemi M, Dehpour AR. Involvement of nitrergic system in the anticonvulsant effect of the cannabinoid CB 1 agonist ACEA in the pentylenetetrazole-induced seizure in mice. Epilepsy research, (2009); 84(2): 110-119.

Moezi L, Shafaroodi H, Hassanipour M, Fakhrzad A, Hassanpour S, et al. Chronic administration of atorvastatin induced anti-convulsant effects in mice: The role of nitric oxide. Epilepsy & Behavior, (2012); 23(4): 399-404.

Shafaroodi H, Moezi L, Fakhrzad A, Hassanipour M, Rezayat M, et al. The involvement of nitric oxide in the anti-seizure effect of acute atorvastatin treatment in mice. Neurological research, (2012); 34(9): 847-853.

Shafaroodi H, Oveisi S, Hosseini M, Niknahad H, Moezi L. The effect of acute aripiprazole treatment on chemically and electrically induced seizures in mice: The role of nitric oxide. Epilepsy & Behavior, (2015); 48: 35-40.

Moezi L, Hosseini M, Oveisi S, Niknahad H, Shafaroodi H. The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole-and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide. Pharmacology, (2015); 95(5-6): 264-270.

Lesani A, Javadi-Paydar M, Khodadad TK, Asghari-Roodsari A, Shirkhodaei M, et al. Involvement of the nitric oxide pathway in the anticonvulsant effect of tramadol on pentylenetetrazole-induced seizures in mice. Epilepsy & Behavior, (2010); 19(3): 290-295.

Lauretti GR, Ahmad I, Pleuvry B. The activity of opioid analgesics in seizure models utilizing N-methyl–aspartic acid, kainic acid, bicuculline and pentylenetetrazole. Neuropharmacology, (1994); 33(2): 155-160

Bahremand A, Nasrabady SE, Shafaroodi H, Ghasemi M, Dehpour AR. Involvement of nitrergic system in the anticonvulsant effect of the cannabinoid CB1 agonist ACEA in the pentylenetetrazole-induced seizure in mice. Epilepsy research, (2009); 84(2-3): 110-119.


  • There are currently no refbacks.