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Pharmacology and Toxicology Publications


Knowles JK, Helbig I, Metcalf CS, Lubbers LS, Isom LL, Demarest S, Goldberg E, George AL Jr, Lerche H, Weckhuysen S, Whittemore V, Berkovic SF, Lowenstein DH.
Precision medicine for genetic epilepsy on the horizon: recent advances, present challenges and suggestions for continued progress.

Epilepsia. 2022 Jun 18. doi: 10.1111/epi.17332. PMID: 35716052.

Nishi T, Metcalf CS, Fujimoto S, Hasegawa S, Miyamoto M, Sunahara E, Watanabe S, Kondo S, White HS.
Anticonvulsive properties of soticlestat, a novel cholesterol 24-hydroxylase inhibitor.

Epilepsia. 2022 Jun;63(6):1580-1590.  doi:10.1111/epi.17232. Epub 2022 Mar 30. PMID: 35316533

West PJ, Thomson K, Billingsley P, Pruess T, Rueda C, Saunders GW, Smith MD, Metcalf CS, Wilcox KS.
Spontaneous recurrent seizures in an intra-amygdala kainate microinjection model of temporal lobe epilepsy are differentially sensitive to antiseizure drugs.

Exp Neurol. 2022 Mar;349:113954. doi: 10.1016/j.expneurol.2021.113954. Epub 2021 Dec 17. PMID: 34922908; PMCID: PMC8815304.

Metcalf CS, Vanegas F, Underwood T, Johnson K, West PJ, Smith MD, Wilcox KS.
Screening of prototype antiseizure and anti-inflammatory compounds in the Theiler's murine encephalomyelitis virus model of epilepsy.

Epilepsia Open. 2022 Mar;7(1):46-58. doi: 10.1002/epi4.12550. Epub 2021 Nov 3. PMID: 34668659; PMCID: PMC8886069.

Heruye SH, Warren TJ, Kostansek Iv JA, Draves SB, Matthews SA, West PJ, Simeone KA, Simeone TA.
Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices.

Nutrients. 2022 Jan 30;14(3):613. doi:10.3390/nu14030613. PMID: 35276972; PMCID: PMC8839482.

Gibson AS, West PJ, Keefe KA.
Effects of methamphetamine-induced neurotoxicity on striatal long-term potentiation.

Psychopharmacology (Berl). 2022 Jan;239(1):93-104. doi: 10.1007/s00213-021-06055-8. Epub 2022 Jan 5. PMID: 34985532; PMCID: PMC8728478.

DePaula-Silva AB, Bell LA, Wallis GJ, Wilcox KS.
Inflammation Unleashed in Viral-Induced Epileptogenesis.

Epilepsy Currents. 2021;21(6):433-440. doi:10.1177/15357597211040939 PMID: 34924851; PMCID: PMC8652320.

Barker-Haliski M, Knox K, Zierath D, Koneval Z, Metcalf C, Wilcox KS, White HS.
Development of an antiepileptogenesis drug screening platform: Effects of everolimus and phenobarbital.

Epilepsia. 2021 Jul;62(7):1677-1688. doi: 10.1111/epi.16955. Epub 2021 Jun 2. PMID: 34080183; PMCID: PMC8260451.

Pernici CD, Mensah JA, Dahle EJ, Johnson KJ, Handy L, Buxton L, Smith MD, West PJ, Metcalf CS, Wilcox KS.
Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program.

Epilepsia. 2021 Jul;62(7):1665-1676. doi: 10.1111/epi.16925. Epub 2021 May 17. PMID: 34002394; PMCID: PMC8360068.

Galanopoulou AS, Löscher W, Lubbers L, O'Brien TJ, Staley K, Vezzani A, D'Ambrosio R, White HS, Sontheimer H, Wolf JA, Twyman R, Whittemore V, Wilcox KS, Klein B.
Antiepileptogenesis and disease modification: Progress, challenges, and the path forward-Report of the Preclinical Working Group of the 2018 NINDS-sponsored antiepileptogenesis and disease modification workshop.

Epilepsia Open. 2021 Jun;6(2):276-296. doi: 10.1002/epi4.12490. Epub 2021 May 6. PMID: 34033232; PMCID: PMC8166793.

Simonato M, Agoston DV, Brooks-Kayal A, Dulla C, Fureman B, Henshall DC, Pitkänen A, Theodore WH, Twyman RE, Kobeissy FH, Wang KK, Whittemore V, Wilcox KS.
Identification of clinically relevant biomarkers of epileptogenesis - a strategic roadmap.

Nat Rev Neurol. 2021 Feb 16. doi: 10.1038/s41582-021-00461-4. Epub ahead of print. PMID: 33594276.

Thomson KE, Metcalf CS, Newell TG, Huff J, Edwards SF, West PJ, Wilcox KS.
Evaluation of Subchronic Administration of Antiseizure Drugs in Spontaneously Seizing Rats. Epilepsia. 2020; 61: 1301– 1311. Epub 2020 May 18. PMID: 32420627; PMCID: PMC7383749.

Bell LA, Wallis GJ, Wilcox KS.
Reactivity and increased proliferation of NG2 cells following central nervous system infection with Theiler's murine encephalomyelitis virus.

Neuroinflammation. 2020 Dec 3;17(1):369. doi: 10.1186/s12974-020-02043-5. PMID: 33272299; PMCID: PMC7713670.

Sawant-Pokam PA, Vail TJ, Metcalf CS, Maguire JL, McKean TO, McKean NO, Brennan KC.
Preventing neuronal edema increases network excitability after traumatic brain injury.

J Clin Invest. 2020 Nov 2;130(11):6005-6020. doi: 10.1172/JCI134793. PMID: 33044227; PMCID: PMC7598047.

Fumeaux NF,  Ebrahim S,  Coughlin BF,  Kadambi A, Azmi A, Xu JX,  Jaoude MA, Nagaraj SB,  Thomson KE,  Newell TG,  Metcalf CS, Wilcox KS,  Kimchi EY, Moraes MFD,  Cash SS. 
Accurate detection of spontaneous seizures using a generalized linear model with external validation. 

Epilepsia. 2020 Sep;61(9):1906-1918. doi: 10.1111/epi.16628. Epub 2020 Aug 6. PMID: 32761902; PMCID: PMC7953845.

Li X, Himes RA, Prosser LC, Christie CF, Watt E, Edwards SF, Metcalf CS, West PJ, Wilcox KS, Chan SSL, and Chou CJ. 
Discovery of the first Vitamin K analog as a potential treatment of pharmacoresistant seizures.

J Med Chem. 2020 Jun 11;63(11):5865-5878. doi: 10.1021/acs.jmedchem.0c00168. Epub 2020 May 22. PMID: 32390424; PMCID: PMC7684765.

Clarkson C, Smeal RM, Hasenoehrl MG, White JA, Rubio ME, Wilcox KS.
Ultrastructural and functional changes at the tripartite synapse during epileptogenesis in a model of temporal lobe epilepsy.

Exp Neurol. 2020 Apr;326:113196. doi: 10.1016/j.expneurol.2020.113196. Epub 2020 Jan 11. PMID: 31935368; PMCID: PMC7054984.

Wilcox KS, West PJ, Metcalf CS.
The Current Approach of the Epilepsy Therapy Screening Program Contract Site for Identifying Improved Therapies for the Treatment of Pharmacoresistant Seizures in Epilepsy.

Neuropharmacology. 2020 Apr;166:107811. doi: 10.1016/j.neuropharm.2019.107811. Epub 2019 Nov 30. PMID: 31790717; PMCID: PMC7054975.

Loewen JL, Albertini G, Dahle EJ, Sato H, Smolders IJ, Massie A, Wilcox KS.
Genetic and pharmacological manipulation of glial glutamate transporters does not alter infection-induced seizure activity.

Exp Neurol. 2019 Aug;318:50-60. doi: 10.1016/j.expneurol.2019.04.010. Epub 2019 Apr 22. PMID: 31022385.

Metcalf CS, Huff J, Thomson KE, Johnson K, Edwards SF, Wilcox KS.  
Evaluation of antiseizure drug efficacy and tolerability in the rat lamotrigine‐resistant amygdala kindling model.

Epilepsia Open. 2019 Aug 12;4(3):452-463. doi: 10.1002/epi4.12354. PMID: 31440726; PMCID: PMC6698678.

Patel DC, Wallis G, Fujinami RS, Wilcox KS, Smith MD.  
Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus.  

Epilepsia Open. 2019 Jul 19;4(3):431-442. doi: 10.1002/epi4.12351. PMID: 31440724; PMCID: PMC6698680.

Metcalf CS, Huntsman M, Garcia G, Kochanski AK, Chikinda M, Watanabe E, Underwood T, Vanegas F, Smith MD, White HS, Bulaj G.
Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs.

Front Neurol. 2019 Mar 27;10:277. doi: 10.3389/fneur.2019.00277. PMID: 30972009; PMCID: PMC6446215.

Umpierre AD, West PJ, White JA, and Wilcox KS. 
Conditional knock-out of mGluR5 from astrocytes during epilepsy development impairs high-frequency glutamate uptake. 

J Neurosci. 2019 Jan 23;39(4):727-742. doi: 10.1523/JNEUROSCI.1148-18.2018. Epub 2018 Nov 30. PMID: 30504280

West PJ, Saunders GW, Billingsley P, Smith MD, White HS, Metcalf CS, Wilcox KS.
Recurrent Epileptiform Discharges in the Medial Entorhinal Cortex of Kainate-Treated Rats Are Differentially Sensitive to Anti-Seizure Drugs.

Epilepsia. 2018 Nov;59(11):2035-2048. doi: 10.1111/epi.14563. Epub 2018 Oct 17. PMID: 30328622; PMCID: PMC6215509.

Nagarajan N, Anderson JS, Jones BW, West PJ, Vachet C, McKay A, Abdullah O, Smith LF, Lipio J, Matsuoka S, Gerig G, Marc R, and Capecchi MR.
Corticostriatal circuit defects in Hoxb8 mutant mice.  

Mol Psychiatry. 2018 Sep;23(9):1868-1877. doi: 10.1038/mp.2017.180. Epub 2017 Sep 26. Erratum in: Mol Psychiatry. 2017 Nov 28;: PMID: 28948967; PMCID: PMC5970001.

Scharfman HE, Kanner AM, Friedman A, Blümcke I, Crocker CE, Cendes F, Diaz-Arrastia R, Förstl H, Fenton AA, Grace AA, Palop J, Morrison J, Nehlig A, Prasad A, Wilcox KS, Jette N, Pohlmann-Eden B.  
Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research? 

Epilepsy Behav. 2018 Jan;78:302-312. doi: 10.1016/j.yebeh.2017.09.016. Epub 2017 Oct 31. PMID: 29097123; PMCID: PMC5756681.

Patel DC, Wilcox KS, Metcalf CS.
Novel Targets for Developing Antiseizure and, Potentially, Antiepileptogenic Drugs.

Epilepsy Curr. 2017 Sep-Oct;17(5):293-298. doi: 10.5698/1535-7597.17.5.293. PMID: 29225544; PMCID: PMC5716500.

Remigio GJ, Loewen JL, Heuston S, Helgeson C, White HS, Wilcox KS, and West PJ.
Corneal Kindled C57bl/6 Mice Exhibit Saturated Dentate Gyrus Long-Term Potentiation and Associated Memory Deficits in the Absence of Overt Neuron Loss.

Neurobiol Dis. 2017 Sep;105:221-234. doi: 10.1016/j.nbd.2017.06.006. Epub 2017 Jun 15. PMID: 28624414; PMCID: PMC5538573.

Basu R, Duan X, Taylor MR, Martin EA, Muralidhar S, Wang Y, Gangi-Wellman L, Das SC, Yamagata M, West PJ, Sanes JR, Williams ME.
Heterophilic Type II Cadherins Are Required for High-Magnitude Synaptic Potentiation in the Hippocampus.

Neuron. 2017 Sep 27;96(1):160-176.e8. doi: 10.1016/j.neuron.2017.09.009. Erratum in: Neuron. 2018 May 2;98 (3):658-668. PMID: 28957665; PMCID: PMC5634529.

Lin Z, Smith MD, Concepcion GP, Haygood MG, Olivera BM, Light A, and Schmidt EW.
Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products.

J Nat Prod. 2017 Aug 25;80(8):2360-2370. doi: 10.1021/acs.jnatprod.7b00317. Epub 2017 Jul 26. PMID: 28745513; PMCID: PMC6025773.

Klein BD, Jacobson CA, Metcalf CS, Smith MD, Wilcox KS, Hampson AJ, and Kehne JH.
Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).

Neurochem Res. 2017 Jul;42(7):1939-1948. doi: 10.1007/s11064-017-2287-8. Epub 2017 May 6. PMID: 28478594.

Metcalf CS, Smith MD, Klein BD, McDougle DR, Zhang L, and Bulaj G.
Preclinical Analgesic and Safety Evaluation of the GalR2-Preferring Analog, NAX 810-2.

Neurochem Res. 2017 Jul;42(7):1983-1994. doi: 10.1007/s11064-017-2229-5. Epub 2017 Apr 6. PMID: 28382595; PMCID: PMC5505798.

Barker-Haliski ML, Johnson K, Billingsley P, Huff J, Handy LJ, Khaleel R, Lu Z, Mau MJ, Pruess TH, Rueda C, Saunders G, Underwood TK, Vanegas F, Smith MD, West PJ, Wilcox KS.
Validation of a Preclinical Drug Screening Platform for Pharmacoresistant Epilepsy.

Neurochem Res. 2017 Jul;42(7):1904-1918. doi: 10.1007/s11064-017-2227-7. Epub 2017 Mar 16. PMID: 28303498; PMCID: PMC7895462.

Smith MD, Woodhead JH, Handy LJ, Pruess TH, Vanegas F, Grussendorf E, Grussendorf J, White K, Bulaj KK, Krumin RK, Hunt M, Wilcox KS.
Preclinical Comparison of Mechanistically Different Antiseizure, Antinociceptive, and/or Antidepressant Drugs in a Battery of Rodent Models of Nociceptive and Neuropathic Pain.

Neurochem Res. 2017 Jul;42(7):1995-2010. doi: 10.1007/s11064-017-2286-9. Epub 2017 May 15. PMID: 28508174.

Metcalf CS, West PJ, Thomson KE, Edwards SF, Smith MD, White HS, and Wilcox KS.
Development and Pharmacologic Characterization of the Rat 6 Hz Model of Partial Seizures

Epilepsia. 2017 Jun;58(6):1073-1084. doi: 10.1111/epi.13764. Epub 2017 Apr 27. PMID: 28449218; PMCID: PMC5469205.

Thomson KE, Modi AC, Glauser TA, Rausch JR, and White HS.
The Impact of Nonadherence to Antiseizure Drugs on Seizure Outcomes in an Animal Model of Epilepsy

Epilepsia. 2017 Jun;58(6):1054-1062. doi: 10.1111/epi.13742. Epub 2017 Apr 12. PMID: 28401980.

Patel DC, Wallis G, Dahle EJ, McElroy PB, Thomson KE, Tesi RJ, Szymkowski DE, West PJ, Smeal RM, Patel M, Fujinami RS, White HS, Wilcox KS.
Hippocampal Tnfα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.

eNeuro. 2017 May 9;4(2):ENEURO.0105-17.2017. doi: 10.1523/ENEURO.0105-17.2017. PMID: 28497109; PMCID: PMC5422919.

Kaufmann D, West PJ, Smith MD, Yagen B, Bialer M, Devor M, White HS, and Brennan KC.
Sec-Butylpropylacetamide (Spd), a New Amide Derivative of Valproic Acid for the Treatment of Neuropathic and Inflammatory Pain.

Pharmacol Res. 2017 Mar;117:129-139. doi: 10.1016/j.phrs.2016.11.030. Epub 2016 Nov 24. PMID: 27890817; PMCID: PMC5352298.

Metcalf CS, Klein BD, Smith MD, Pruess T, Ceusters T, Lavreysen H, Pype S, Van Ossalaer N, Twyman R, White HS.  
Efficacy of Mglu2-Positive Allosteric Modulators Alone and in Combination with Levetiracetam in the Mouse 6 Hz Model of Psychomotor Seizures.

Epilepsia. 2017 Mar;58(3):484-493. doi: 10.1111/epi.13659. Epub 2017 Feb 6. PMID: 28166368.

Metcalf CS, Klein BD, McDougle DR, Zhang L, Kaufmann D, Bulaj G, White HS.
Preclinical evaluation of intravenous NAX 810-2, a novel GalR2-preferring analog, for anticonvulsant efficacy and pharmacokinetics.

Epilepsia. 2017 Feb;58(2):239-246. doi: 10.1111/epi.13647. Epub 2017 Jan 18. PMID: 28098336; PMCID: PMC5291807.

Barker-Haliski ML, Heck TD, Dahle EJ, Vanegas F, Pruess TH, Wilcox KS, and White HS.
Acute Treatment with Minocycline, but Not Valproic Acid, Improves Long-Term Behavioral Outcomes in the Theiler's Virus Model of Temporal Lobe Epilepsy.

Epilepsia. 2016 Dec;57(12):1958-1967. doi: 10.1111/epi.13577. Epub 2016 Oct 14. PMID: 27739576; PMCID: PMC5154893.

Gibbons MB, Wilcox KS.
Could Astrocytes Be Used to Beat Epilepsy Experiments in dnSNARE Mice Drum Up New Hope.
Epilepsy Curr. 2014 Sep;14(5):277-8. doi: 10.5698/1535-7597-14.5.277. No abstract available.

Gee JM, Smith NA, Fernandez FR, Economo MN, Brunert D, Rothermel M, Morris SC, Talbot A, Palumbos S, Ichida JM, Shepherd JD, West PJ, Wachowiak M, Capecchi MR, Wilcox KS, White JA, Tvrdik P.
Imaging activity in neurons and glia with a Polr2a-based and cre-dependent GCaMP5G-IRES-tdTomato reporter mouse.
Neuron. 2014 Sep 3;83(5):1058-72. doi: 10.1016/j.neuron.2014.07.024. Epub 2014 Aug 21.

Simonato M, Brooks-Kayal AR, Engel J Jr, Galanopoulou AS, Jensen FE, Moshé SL, O'Brien TJ, Pitkanen A, Wilcox KS, French JA.
The challenge and promise of anti-epileptic therapy development in animal models.
Lancet Neurol. 2014 Sep;13(9):949-60. doi: 10.1016/S1474-4422(14)70076-6. Epub 2014 Aug 10. Review.

Wilcox KS, Vezzani A.
Does brain inflammation mediate pathological outcomes in epilepsy?
Adv Exp Med Biol. 2014;813:169-83. doi: 10.1007/978-94-017-8914-1_14. Review.

Vargas JR, Takahashi DK, Thomson KE, Wilcox KS.
The expression of kainate receptor subunits in hippocampal astrocytes after experimentally induced status epilepticus.
J Neuropathol Exp Neurol. 2013 Oct;72(10):919-32. doi: 10.1097/NEN.0b013e3182a4b266.

Rogawski MA, Tofighy A, White HS, Matagne A, Wolff C.
Current understanding of the mechanism of action of the antiepileptic drug lacosamide.
Epilepsy Res. 2015 Feb;110C:189-205. doi: 10.1016/j.eplepsyres.2014.11.021. Epub 2014 Dec 3. Review.

Barker-Haliski M, Friedman D, White HS, French JA.
How clinical development can, and should, inform translational science.
Neuron. 2014 Nov 5;84(3):582-93. doi: 10.1016/j.neuron.2014.10.029. Epub 2014 Nov 5. Review.

Metcalf CS, Klein BD, McDougle DR, Zhang L, Smith MD, Bulaj G, White HS.
Analgesic properties of a peripherally acting and GalR2 receptor-preferring galanin analog in inflammatory, neuropathic, and acute pain models.
J Pharmacol Exp Ther. 2015 Jan;352(1):185-93. doi: 10.1124/jpet.114.219063. Epub 2014 Oct 27.

Thomson KE, White HS.
A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models.
J Neurosci Methods. 2014 Dec 30;238:105-11. doi: 10.1016/j.jneumeth.2014.09.019. Epub 2014 Sep 26.

Barker-Haliski M, Sills GJ, White HS.
What are the arguments for and against rational therapy for epilepsy?
Adv Exp Med Biol. 2014;813:295-308. doi: 10.1007/978-94-017-8914-1_24. Review.

Schousboe A, Madsen KK, Barker-Haliski ML, White HS.
The GABA synapse as a target for antiepileptic drugs: a historical overview focused on GABA transporters.
Neurochem Res. 2014 Oct;39(10):1980-7. doi: 10.1007/s11064-014-1263-9. Epub 2014 Mar 14.

West PJ, Saunders GW, Remigio GJ, Wilcox KS, White HS.
Antiseizure drugs differentially modulate θ-burst induced long-term potentiation in C57BL/6 mice.
Epilepsia. 2014 Feb;55(2):214-23. doi: 10.1111/epi.12524. Epub 2014 Jan 21.

White HS, Löscher W.
Searching for the ideal antiepileptogenic agent in experimental models: single treatment versus combinatorial treatment strategies.
Neurotherapeutics. 2014 Apr;11(2):373-84. doi: 10.1007/s13311-013-0250-1. Review.

Umpierre AD, Remigio GJ, Dahle EJ, Bradford K, Alex AB, Smith MD, West PJ, White HS, Wilcox KS.
Impaired cognitive ability and anxiety-like behavior following acute seizures in the Theiler's virus model of temporal lobe epilepsy.
Neurobiol Dis. 2014 Apr;64:98-106. doi: 10.1016/j.nbd.2013.12.015. Epub 2014 Jan 9.

Jequier Gygax M, Klein BD, White HS, Kim M, Galanopoulou AS.
Efficacy and tolerability of the galanin analog NAX 5055 in the multiple-hit rat model of symptomatic infantile spasms.
Epilepsy Res. 2014 Jan;108(1):98-108. doi: 10.1016/j.eplepsyres.2013.10.015. Epub 2013 Oct 28.