{
    "nodes": [
        [
            "Brugada syndrome 5",
            "DISEASE"
        ],
        [
            "Tetrodotoxin",
            "DRUG"
        ],
        [
            "gamma-Aminobutyric Acid",
            "DRUG"
        ],
        [
            "Lidocaine",
            "DRUG"
        ],
        [
            "Valproic Acid",
            "DRUG"
        ],
        [
            "Cannabidiol",
            "DRUG"
        ],
        [
            "Levobupivacaine",
            "DRUG"
        ],
        [
            "Phenytoin",
            "DRUG"
        ],
        [
            "Lacosamide",
            "DRUG"
        ],
        [
            "Carbamazepine",
            "DRUG"
        ],
        [
            "vinpocetine",
            "DRUG"
        ],
        [
            "SCN1B",
            "GENE"
        ]
    ],
    "edges": [
        [
            [
                "SCN1B",
                "Phenytoin"
            ],
            0.12417014000000001,
            [
                [
                    "Chih-Hsiang Lin, Chen-Jui Ho, Yan-Ting Lu, Meng-Han Tsai (2021). Response to Sodium Channel blocking Antiseizure medications and coding polymorphisms of Sodium Channel genes in Taiwanese epilepsy patients. BMC neurology, 367. https://doi.org/10.1186/s12883-021-02395-2 PMID: 34556045",
                    "34556045"
                ],
                [
                    "Louis T Dang, Shane C Quinonez, Bridget R Becka, Lori L Isom, Sucheta M Joshi (2020). Dramatic Improvement in Seizures With Phenytoin Treatment in an Individual With Refractory Epilepsy and a SCN1B Variant. Pediatric neurology, 121-122. https://doi.org/10.1016/j.pediatrneurol.2020.03.012 PMID: 32303391",
                    "32303391"
                ],
                [
                    "Tariq Zaman, Ingo Helbig, Ivana Babić Božović, Suzanne D DeBrosse, A Christina Bergqvist, Kimberly Wallis, Livija Medne, Aleš Maver, Borut Peterlin, Katherine L Helbig, Xiaohong Zhang, Ethan M Goldberg (2018). Mutations in SCN3A cause early infantile epileptic encephalopathy. Annals of neurology, 703-717. https://doi.org/10.1002/ana.25188 PMID: 29466837",
                    "29466837"
                ],
                [
                    "Xin Zhou, Yue-Chen Luo, Wen-Jie Ji, Li Zhang, Yan Dong, Lan Ge, Rui-Yi Lu, Hai-Ying Sun, Zao-Zeng Guo, Guo-Hong Yang, Tie-Min Jiang, Yu-Ming Li (2013). Modulation of mononuclear phagocyte inflammatory response by liposome-encapsulated voltage gated sodium channel inhibitor ameliorates myocardial ischemia/reperfusion injury in rats. PloS one, e74390. https://doi.org/10.1371/journal.pone.0074390 PMID: 24069305",
                    "24069305"
                ],
                [
                    "Sandeep Grover, Mandaville Gourie-Devi, Ruchi Baghel, Sangeeta Sharma, Kiran Bala, Meena Gupta, Krishnamoorthy Narayanasamy, Binuja Varma, Meenal Gupta, Kavita Kaur, Puneet Talwar, Harpreet Kaur, Sudheer Giddaluru, Abhay Sharma, Samir K Brahmachari,  Indian Genome Variation Consortium, Ritushree Kukreti (2010). Genetic profile of patients with epilepsy on first-line antiepileptic drugs and potential directions for personalized treatment. Pharmacogenomics, 927-41. https://doi.org/10.2217/pgs.10.62 PMID: 20602612",
                    "20602612"
                ],
                [
                    "Paul T Lucas, Laurence S Meadows, Jane Nicholls, David S Ragsdale (2005). An epilepsy mutation in the beta1 subunit of the voltage-gated sodium channel results in reduced channel sensitivity to phenytoin. Epilepsy research, 77-84. https://doi.org/10.1016/j.eplepsyres.2005.03.003 PMID: 15922564",
                    "15922564"
                ]
            ]
        ],
        [
            [
                "SCN1B",
                "Valproic Acid"
            ],
            0.08278009,
            [
                [
                    "Chih-Hsiang Lin, Chen-Jui Ho, Yan-Ting Lu, Meng-Han Tsai (2021). Response to Sodium Channel blocking Antiseizure medications and coding polymorphisms of Sodium Channel genes in Taiwanese epilepsy patients. BMC neurology, 367. https://doi.org/10.1186/s12883-021-02395-2 PMID: 34556045",
                    "34556045"
                ],
                [
                    "Raidah S Al-Baradie (2013). Dravet syndrome, what is new? Neurosciences (Riyadh, Saudi Arabia), 11-7. PMID: 23291792",
                    "23291792"
                ],
                [
                    "Sandeep Grover, Mandaville Gourie-Devi, Ruchi Baghel, Sangeeta Sharma, Kiran Bala, Meena Gupta, Krishnamoorthy Narayanasamy, Binuja Varma, Meenal Gupta, Kavita Kaur, Puneet Talwar, Harpreet Kaur, Sudheer Giddaluru, Abhay Sharma, Samir K Brahmachari,  Indian Genome Variation Consortium, Ritushree Kukreti (2010). Genetic profile of patients with epilepsy on first-line antiepileptic drugs and potential directions for personalized treatment. Pharmacogenomics, 927-41. https://doi.org/10.2217/pgs.10.62 PMID: 20602612",
                    "20602612"
                ],
                [
                    "Berten Ceulemans, Marc Boel, Lieve Claes, Lina Dom, Herman Willekens, Paul Thiry, Lieven Lagae (2004). Severe myoclonic epilepsy in infancy: toward an optimal treatment. Journal of child neurology, 516-21. https://doi.org/10.1177/08830738040190070701 PMID: 15526956",
                    "15526956"
                ]
            ]
        ],
        [
            [
                "SCN1B",
                "vinpocetine"
            ],
            0.21322143
        ],
        [
            [
                "SCN1B",
                "Carbamazepine"
            ],
            0.16556018,
            [
                [
                    "Chih-Hsiang Lin, Chen-Jui Ho, Yan-Ting Lu, Meng-Han Tsai (2021). Response to Sodium Channel blocking Antiseizure medications and coding polymorphisms of Sodium Channel genes in Taiwanese epilepsy patients. BMC neurology, 367. https://doi.org/10.1186/s12883-021-02395-2 PMID: 34556045",
                    "34556045"
                ],
                [
                    "Soha Namazi, Negar Azarpira, Katayoon Javidnia, Mehrdad Emami, Rahimeh Rahjoo, Razieh Berahmand, Afshin Borhani-Haghighi (2015). SCN1A and SCN1B gene polymorphisms and their association with plasma concentrations of carbamazepine and carbamazepine 10, 11 epoxide in Iranian epileptic patients. Iranian journal of basic medical sciences, 1215-20. PMID: 26877851",
                    "26877851"
                ],
                [
                    "Anna Doeser, Patricio Soares-da-Silva, Heinz Beck, Mischa Uebachs (2014). The effects of eslicarbazepine on persistent Na⁺ current and the role of the Na⁺ channel β subunits. Epilepsy research, 202-11. PMID: 24368131",
                    "24368131"
                ],
                [
                    "Robert J Hatch, Christopher A Reid, Steven Petrou (2014). Enhanced in vitro CA1 network activity in a sodium channel β1(C121W) subunit model of genetic epilepsy. Epilepsia, 601-8. https://doi.org/10.1111/epi.12568 PMID: 24605816",
                    "24605816"
                ],
                [
                    "Mischa Uebachs, Christina Albus, Thoralf Opitz, Lori Isom, Isabelle Niespodziany, Christian Wolff, Heinz Beck (2012). Loss of β1 accessory Na+ channel subunits causes failure of carbamazepine, but not of lacosamide, in blocking high-frequency firing via differential effects on persistent Na+ currents. Epilepsia, 1959-67. https://doi.org/10.1111/j.1528-1167.2012.03675.x PMID: 23016711",
                    "23016711"
                ],
                [
                    "S Yamashita, A Okumura, T Yamamoto, K Shimojima, T Tanabe, T Shimizu (2011). SCN1B is not related to benign partial epilepsy in infancy or convulsions with gastroenteritis. Neuropediatrics, 135-7. https://doi.org/10.1055/s-0031-1285837 PMID: 21882141",
                    "21882141"
                ],
                [
                    "Mischa Uebachs, Thoralf Opitz, Michel Royeck, Gesa Dickhof, Marie-Therese Horstmann, Lori L Isom, Heinz Beck (2010). Efficacy loss of the anticonvulsant carbamazepine in mice lacking sodium channel beta subunits via paradoxical effects on persistent sodium currents. The Journal of neuroscience : the official journal of the Society for Neuroscience, 8489-501. https://doi.org/10.1523/JNEUROSCI.1534-10.2010 PMID: 20573896",
                    "20573896"
                ],
                [
                    "Sandeep Grover, Mandaville Gourie-Devi, Ruchi Baghel, Sangeeta Sharma, Kiran Bala, Meena Gupta, Krishnamoorthy Narayanasamy, Binuja Varma, Meenal Gupta, Kavita Kaur, Puneet Talwar, Harpreet Kaur, Sudheer Giddaluru, Abhay Sharma, Samir K Brahmachari,  Indian Genome Variation Consortium, Ritushree Kukreti (2010). Genetic profile of patients with epilepsy on first-line antiepileptic drugs and potential directions for personalized treatment. Pharmacogenomics, 927-41. https://doi.org/10.2217/pgs.10.62 PMID: 20602612",
                    "20602612"
                ]
            ]
        ],
        [
            [
                "Brugada syndrome 5",
                "SCN1B"
            ],
            7.682499
        ],
        [
            [
                "SCN1B",
                "Tetrodotoxin"
            ],
            0.31042533,
            [
                [
                    "Joohee Park, Coralyne Proux, William Ehanno, Léa Réthoré, Emilie Vessières, Jennifer Bourreau, Julie Favre, Gilles Kauffenstein, César Mattei, Hélène Tricoire-Leignel, Daniel Henrion, Claire Legendre, Christian Legros (2023). Tetrodotoxin Decreases the Contractility of Mesenteric Arteries, Revealing the Contribution of Voltage-Gated Na+ Channels in Vascular Tone Regulation. Marine drugs. https://doi.org/10.3390/md21030196 PMID: 36976245",
                    "36976245"
                ],
                [
                    "Jacob M Hull, Nicholas Denomme, Yukun Yuan, Victoria Booth, Lori L Isom (2023). Heterogeneity of voltage gated sodium current density between neurons decorrelates spiking and suppresses network synchronization in Scn1b null mouse models. Scientific reports, 8887. https://doi.org/10.1038/s41598-023-36036-0 PMID: 37264112",
                    "37264112"
                ],
                [
                    "Alexander S Haworth, Samantha L Hodges, Alina L Capatina, Lori L Isom, Christoph G Baumann, William J Brackenbury (2022). Subcellular dynamics and functional activity of the cleaved intracellular domain of the Na+ channel β1 subunit. The Journal of biological chemistry, 102174. https://doi.org/10.1016/j.jbc.2022.102174 PMID: 35752364",
                    "35752364"
                ],
                [
                    "Huaizong Shen, Dongliang Liu, Kun Wu, Jianlin Lei, Nieng Yan (2019). Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. Science (New York, N.Y.), 1303-1308. https://doi.org/10.1126/science.aaw2493 PMID: 30765606",
                    "30765606"
                ],
                [
                    "Kohei Takahara, Tadashi Yamamoto, Keiichiro Uchida, Hai-Lei Zhu, Atsushi Shibata, Tetsuichiro Inai, Mitsuru Noguchi, Mari Yotsu-Yamashita, Noriyoshi Teramoto (2018). Effects of 4,9-anhydrotetrodotoxin on voltage-gated Na+ channels of mouse vas deferens myocytes and recombinant NaV1.6 channels. Naunyn-Schmiedeberg's archives of pharmacology, 489-499. https://doi.org/10.1007/s00210-018-1476-6 PMID: 29453527",
                    "29453527"
                ],
                [
                    "Xianming Lin, Heather O'Malley, Chunling Chen, David Auerbach, Monique Foster, Akshay Shekhar, Mingliang Zhang, William Coetzee, José Jalife, Glenn I Fishman, Lori Isom, Mario Delmar (2015). Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts. The Journal of physiology, 1389-407. https://doi.org/10.1113/jphysiol.2014.277699 PMID: 25772295",
                    "25772295"
                ],
                [
                    "Xin Huang, Yuan Du, Pei Yang, Shienfong Lin, Yutao Xi, Zhao Yang, Aiqun Ma (2015). Age-dependent alterations of voltage-gated Na(+) channel isoforms in rat sinoatrial node. Mechanisms of ageing and development, 80-90. PMID: 26528804",
                    "26528804"
                ],
                [
                    "Sabrina Kraus, Bernadette Lehner, Nadine Reichhart, Sebastien Couillard-Despres, Katrin Wagner, Ulrich Bogdahn, Ludwig Aigner, Olaf Strauß (2013). Transforming growth factor-β1 primes proliferating adult neural progenitor cells to electrophysiological functionality. Glia, 1767-83. https://doi.org/10.1002/glia.22551 PMID: 24038377",
                    "24038377"
                ],
                [
                    "Everardo Hernandez-Plata, Cindy S Ortiz, Brenda Marquina-Castillo, Ingrid Medina-Martinez, Ana Alfaro, Jaime Berumen, Manuel Rivera, Juan C Gomora (2012). Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer. International journal of cancer, 2013-23. https://doi.org/10.1002/ijc.26210 PMID: 21630263",
                    "21630263"
                ],
                [
                    "William J Brackenbury, Jeffrey D Calhoun, Chunling Chen, Haruko Miyazaki, Nobuyuki Nukina, Fumitaka Oyama, Barbara Ranscht, Lori L Isom (2010). Functional reciprocity between Na+ channel Nav1.6 and beta1 subunits in the coordinated regulation of excitability and neurite outgrowth. Proceedings of the National Academy of Sciences of the United States of America, 2283-8. https://doi.org/10.1073/pnas.0909434107 PMID: 20133873",
                    "20133873"
                ]
            ]
        ],
        [
            [
                "SCN1B",
                "Lacosamide"
            ],
            0.27530652,
            [
                [
                    "Chih-Hsiang Lin, Chen-Jui Ho, Yan-Ting Lu, Meng-Han Tsai (2021). Response to Sodium Channel blocking Antiseizure medications and coding polymorphisms of Sodium Channel genes in Taiwanese epilepsy patients. BMC neurology, 367. https://doi.org/10.1186/s12883-021-02395-2 PMID: 34556045",
                    "34556045"
                ],
                [
                    "Tariq Zaman, Ingo Helbig, Ivana Babić Božović, Suzanne D DeBrosse, A Christina Bergqvist, Kimberly Wallis, Livija Medne, Aleš Maver, Borut Peterlin, Katherine L Helbig, Xiaohong Zhang, Ethan M Goldberg (2018). Mutations in SCN3A cause early infantile epileptic encephalopathy. Annals of neurology, 703-717. https://doi.org/10.1002/ana.25188 PMID: 29466837",
                    "29466837"
                ],
                [
                    "Mischa Uebachs, Christina Albus, Thoralf Opitz, Lori Isom, Isabelle Niespodziany, Christian Wolff, Heinz Beck (2012). Loss of β1 accessory Na+ channel subunits causes failure of carbamazepine, but not of lacosamide, in blocking high-frequency firing via differential effects on persistent Na+ currents. Epilepsia, 1959-67. https://doi.org/10.1111/j.1528-1167.2012.03675.x PMID: 23016711",
                    "23016711"
                ]
            ]
        ],
        [
            [
                "SCN1B",
                "gamma-Aminobutyric Acid"
            ],
            0.08311199,
            [
                [
                    "Yukun Yuan, Heather A O'Malley, Melissa A Smaldino, Alexandra A Bouza, Jacob M Hull, Lori L Isom (2019). Delayed maturation of GABAergic signaling in the Scn1a and Scn1b mouse models of Dravet Syndrome. Scientific reports, 6210. https://doi.org/10.1038/s41598-019-42191-0 PMID: 30996233",
                    "30996233"
                ],
                [
                    "Sy Vinh Le, Phan Hoang Truc Le, Thi Khanh Van Le, Thi Thuy Kieu Huynh, Thi Thu Hang Do (2017). A mutation in GABRB3 associated with Dravet syndrome. American journal of medical genetics. Part A, 2126-2131. https://doi.org/10.1002/ajmg.a.38282 PMID: 28544625",
                    "28544625"
                ],
                [
                    "Sabrina Kraus, Bernadette Lehner, Nadine Reichhart, Sebastien Couillard-Despres, Katrin Wagner, Ulrich Bogdahn, Ludwig Aigner, Olaf Strauß (2013). Transforming growth factor-β1 primes proliferating adult neural progenitor cells to electrophysiological functionality. Glia, 1767-83. https://doi.org/10.1002/glia.22551 PMID: 24038377",
                    "24038377"
                ],
                [
                    "Hui Hui Sun, Yue Hua Zhang (2008). [Progress in molecular genetics of generalized epilepsy with febrile seizures plus]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences, 229-33. PMID: 18458705",
                    "18458705"
                ]
            ]
        ],
        [
            [
                "SCN1B",
                "Lidocaine"
            ],
            0.08278009,
            [
                [
                    "Iris S Brummelhuis, Stephen J Fiascone, Kathleen T Hasselblatt, Gyorgy Frendl, Kevin M Elias (2021). Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer. Cancers. https://doi.org/10.3390/cancers13215437 PMID: 34771603",
                    "34771603"
                ],
                [
                    "Wandi Zhu, Wei Wang, Paweorn Angsutararux, Rebecca L Mellor, Lori L Isom, Jeanne M Nerbonne, Jonathan R Silva (2021). Modulation of the effects of class Ib antiarrhythmics on cardiac NaV1.5-encoded channels by accessory NaVβ subunits. JCI insight. PMID: 34156986",
                    "34156986"
                ],
                [
                    "Mika Nakazawa, Akihisa Okumura, Shinichi Niijima, Shintaro Yamashita, Kuriko Shimono, Shinichi Hirose, Toshiaki Shimizu (2013). Oral mexiletine for lidocaine-responsive neonatal epilepsy. Brain & development, 667-9. PMID: 23182886",
                    "23182886"
                ],
                [
                    "R Ogawa, R Kishi, A Takagi, I Sakaue, H Takahashi, N Matsumoto, K Masuhara, K Nakazawa, S Kobayashi, F Miyake, H Echizen (2010). A novel microsatellite polymorphism of sodium channel beta1-subunit gene (SCN1B) may underlie abnormal cardiac excitation manifested by coved-type ST-elevation compatible with Brugada syndrome in Japanese. International journal of clinical pharmacology and therapeutics, 109-19. https://doi.org/10.5414/cpp48109 PMID: 20137763",
                    "20137763"
                ]
            ]
        ],
        [
            [
                "SCN1B",
                "Levobupivacaine"
            ],
            0.21322143
        ],
        [
            [
                "SCN1B",
                "Cannabidiol"
            ],
            0.27530652,
            [
                [
                    "Changqing Xu, Yumin Zhang, David Gozal, Paul Carney (2021). Channelopathy of Dravet Syndrome and Potential Neuroprotective Effects of Cannabidiol. Journal of central nervous system disease, 11795735211048045. https://doi.org/10.1177/11795735211048045 PMID: 34992485",
                    "34992485"
                ],
                [
                    "Mohammad-Reza Ghovanloo, Noah Gregory Shuart, Janette Mezeyova, Richard A Dean, Peter C Ruben, Samuel J Goodchild (2018). Inhibitory effects of cannabidiol on voltage-dependent sodium currents. The Journal of biological chemistry, 16546-16558. https://doi.org/10.1074/jbc.RA118.004929 PMID: 30219789",
                    "30219789"
                ],
                [
                    "Karen S Ho, E Robert Wassman (2017). A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management. American journal of medical genetics. Part A, 324-326. https://doi.org/10.1002/ajmg.a.37979 PMID: 28102593",
                    "28102593"
                ]
            ]
        ]
    ]
}