Safety and efficacy of eslicarbazepine acetate for seizure prevention in patients with stroke at high risk of developing post-stroke epilepsy

Koepp MJ, Trinka E, Mah YH, Bentes C, Knake S, Gigli GL, Serratosa JM, Zelano J, Simister R, Brigo F, Löscher W, Galovic M, et al.

Lancet Neurol., 25, 256–267, 2026

First clinical trial to study whether eslicarbazepine acetate prevents or reduces the incidence of epilepsy after acute ischemic stroke or acute intracerebral hemorrhage

Intranasal Seletracetam in a Patient with Reading Epilepsy: First-in-Human Use to Prevent Reflex Seizures

Koepp MJ, Poppert KN, Felder T, Thomschewski A, Lafenthaler S, Klein P, Rotenberg A, Löscher W, Rundfeldt C, and Trinka E

Ann. Neurol., 99, 535–539, 2026

First-in-human proof of concept that intranasal seletracetam prevents reflex seizures

Ranking of antiseizure medications in a panel of focal seizure models predicts their comparative efficacy in clinical add-on trials in drug-resistant focal epilepsy

Löscher W and Klein P

Epilepsia, in press, 2026

A new approach for predicting antiseizure efficacy in clinical trials

Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia

Welzel B, Schmidt R, Johne M, and Löscher W

Ann. Neurol., 93, 226–243, 2023

Surprising finding that midazolam prevents the later-in-life adverse outcome of neonatal asphyxia in a rat model

Systematic evaluation of rationally chosen multitargeted drug combinations: a combination of low doses of levetiracetam, atorvastatin and ceftriaxone exerts antiepileptogenic effects in a mouse model of acquired epilepsy

Welzel L, Bergin DH, Schidlitzki A, Twele F, Johne M, Klein P, and Löscher W

Neurobiol. Dis., 149, 105227, 2021

Discovery of a highly effective antiepileptogenic drug cocktail

Proof-of-concept that network pharmacology is effective to modify development of acquired temporal lobe epilepsy

Schidlitzki A, Bascunana P, Srivastava PK, Welzel L, Twele F, Töllner K, Käufer C, Gericke B, Feleke R, Meier M, Polyak A, Ross TL, Gerhauser I, Bankstahl JP, Johnson MR, Bankstahl M, and Löscher W

Neurobiol. Dis., 134, 104664, 2020

First description that a cocktail of multi-targeted drugs prevents epilepsy

The circadian dynamics of the hippocampal transcriptome and proteome is altered in experimental temporal lobe epilepsy

Debski KJ, Ceglia N, Ghestem A, Ivanov AI, Brancati GE, Bröer S, Bot AM, Müller JA, Schoch S, Becker A, Löscher W, Guye M, Sassone-Corsi P, Lukasiuk K, Baldi P, and Bernard C

Science Adv., 6, eaat5979, 2020

The hippocampus operates in a different functioning mode in epilepsy

Association of Piriform Cortex Resection with Surgical Outcomes in Patients with Temporal Lobe Epilepsy

Galovic M, Baudracco I, Wright-Goff E, et al. (incl. Löscher W)

JAMA Neurol., 76, 690–700, 2019

These results support the importance of resecting the piriform cortex in neurosurgical treatment of temporal lobe epilepsy and suggest that this area has a key role in seizure generation

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

Stanelle-Bertram S, Walendy-Gnirss K, Speiseder T, et al. (incl. Löscher W)

Nature Microbiol., 3, 1161–1174, 2018

Description of an important sex difference in the consequences of Zika virus infection

A novel mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils

Noack A, Gericke B, von Köckritz-Blickwede M, Menze A, Noack S, Gerhauser I, Osten F, Naim HY, and Löscher W

PNAS, 115, E9590–E9599, 2018

These findings introduce a novel mechanism that might contribute to brain protection against potentially toxic xenobiotics, including therapeutically important chemotherapeutic drugs

Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures

Käufer C, Chhatbar C, Bröer S, Waltl I, Ghita L, Gerhauser I, Kalinke U, and Löscher W

PNAS, 115, E8929–E8938, 2018

CNS inflammatory mechanism(s) other than the infiltrating myeloid cells trigger the development of seizures during viral encephalitis

Gene therapy decreases seizures in a model of incontinentia pigmenti

Dogbevia GK, Töllner K, Korbelin J, Bröer S, Ridder DA, Grasshoff H, Brandt C, Wenzel J, Straub BK, Trepel M, Löscher W, and Schwaninger M

Ann. Neurol., 82, 93–104, 2017

The study provides evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in incontinentia pigmenti

Single dose efficacy evaluation of two partial benzodiazepine receptor agonists in photosensitive epilepsy patients

Kasteleijn-Nolst Trenité DG, Groenwold RH, Schmidt B, and Löscher W

Epilepsy Res., 122, 30–36, 2016

First clinical trial showing that the partial GABA_A receptor agonist abecarnil exerts antiseizure efficacy

Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy

Bar-Klein G, Klee R, Brandt C, Bankstahl M, Bascunana P, Töllner K, Dalipaj H, Bankstahl JP, Friedman A, and Löscher W

Ann. Neurol., 80, 896–908, 2016

First description that isoflurane is antiepileptogenic

A novel prodrug-based strategy to increase effects of bumetanide in epilepsy

Töllner K, Brandt C, Töpfer M, Brunhofer G, Erker T, Gabriel M, Feit PW, Lindfors J, Kaila K, and Löscher W

Ann. Neurol., 75, 550–562, 2014

The study shows that the goal of designing bumetanide prodrugs that specifically target the brain is feasible

Converging PET and fMRI evidence for a common area involved in human focal epilepsies

Laufs H, Richardson MP, Salek-Haddadi A, Vollmar C, Duncan JS, Gale K, Lemieux L, Löscher W, and Koepp MJ

Neurology, 77, 904–910, 2011

An area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery

A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier

Bankstahl JP, Bankstahl M, Kuntner C, Stanek J, Wanek T, Meier M, Ding XQ, Müller M, Langer O, and Löscher W

J. Neurosci., 31, 8803–8811, 2011

Development of a PET protocol for studying overexpression of P-glycoprotein at the blood-brain barrier of epileptic rats

The anticonvulsant response to valproate in kindled rats is correlated with its effect on neuronal firing in the substantia nigra pars reticulata: a new mechanism of pharmacoresistance

Töllner K, Wolf S, Löscher W, and Gernert M

J. Neurosci., 31, 16423–16434, 2011

Description of a new mechanism of drug resistance

Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy

Brandt C, Nozadze M, Heuchert N, Rattka M, and Löscher W

J. Neurosci., 30, 8602–8612, 2010

A combination of phenobarbital and bumetanide, but neither drug alone, is disease-modifying in a model of focal epilepsy

Neurogenesis in the adult rat piriform cortex

Pekcec A, Löscher W, and Potschka H

Neuroreport, 17, 571–574, 2006

First description that neurogenesis occurs in the adult piriform cortex

The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy

Brandt C, Bethmann K, Gastens AM, and Löscher W

Neurobiol. Dis., 24, 202–211, 2006

First description that inhibition of the efflux drug transporter P-glycoprotein reverses drug resistance in epileptic rats

Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures

Volk HA and Löscher W

Brain, 128, 1358–1368, 2005

First description that the efflux drug transporter P-glycoprotein is increased in rats with pharmacoresistant focal epilepsy

Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures

Löscher W, Potschka H, Rieck S, Tipold A, and Rundfeldt C

Epilepsia, 45, 1228–1239, 2004

First description that the novel partial GABA receptor agonist imepitoin exerts antiseizure effects in epileptic dogs

Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon

Altrock WD, tom Dieck S, Sokolov M, et al. (incl. Löscher W)

Neuron, 37, 787–800, 2003

Bassoon is not essential for synapse formation, but plays an essential role in the regulated neurotransmitter release from a subset of glutamatergic synapses

N-methyl-D-aspartate receptor blockade after status epilepticus protects against limbic brain damage but not against epilepsy in the kainate model of temporal lobe epilepsy

Brandt C, Potschka H, Löscher W, and Ebert U

Neuroscience, 118, 727–740, 2003

First study on the chicken-or-egg causality dilemma of hippocampal sclerosis and epilepsy, indicating that these two phenomena are not causally related

Deficit of striatal parvalbumin-reactive GABAergic interneurons and decreased basal ganglia output in a genetic rodent model of idiopathic paroxysmal dystonia

Gernert M, Hamann M, Bennay M, Löscher W, and Richter A

J. Neurosci., 20, 7052–7058, 2000

Striatal GABAergic neurons are involved in paroxysmal dystonia

Seizure suppression in kindling epilepsy by grafts of fetal GABAergic neurons in rat substantia nigra

Löscher W, Ebert U, Lehmann H, Rosenthal C, and Nikkhah G

J. Neurosci. Res., 51, 196–209, 1998

First successful demonstration that neurotransplantation of fetal GABAergic neurons is anticonvulsant

Amygdala-kindling induces a lasting reduction of GABA-immunoreactive neurons in a discrete area of the ipsilateral piriform cortex

Lehmann H, Ebert U, and Löscher W

Synapse, 29, 299–309, 1998

GABAergic neurons in the piriform cortex are involved in epileptogenesis

A comparison of the effects of valproate and its major active metabolite E-2-en-valproate on single unit activity of substantia nigra pars reticulata neurons in rats

Rohlfs A, Rundfeldt C, Koch R, and Löscher W

J. Pharmacol. Exp. Ther., 277, 1305–1314, 1996

Valproate and its main active metabolite decrease firing of neurons in the substantia nigra pars reticulata

Immunocytochemical localization of GABA immunoreactivity in dentate granule cells of normal and kindled rats

Lehmann H, Ebert U, and Löscher W

Neurosci. Lett., 212, 41–44, 1996

The first description that glutamatergic dentate granule cells also produce GABA

Susceptibility of different cell layers of the anterior and posterior part of the piriform cortex to electrical stimulation and kindling

Löscher W, Ebert U, Wahnschaffe U, and Rundfeldt C

Neuroscience, 66, 265–276, 1995

Characterization of the role of the piriform cortex in temporal lobe epilepsy

Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats

Löscher W and Hönack D

Eur. J. Pharmacol., 232, 147–158, 1993

Description of the unique antiseizure profile of levetiracetam

Plasma GABA and seizure control with vigabatrin

Löscher W, Gram L, and Stefan H

Lancet, 341, 117, 1993

Increases in plasma GABA are correlated with the individual response to vigabatrin

Kindling as a model of drug-resistant epilepsy: Selection of phenytoin-resistant and nonresistant rats

Löscher W and Rundfeldt C

J. Pharmacol. Exp. Ther., 258, 483–489, 1991

The first description of the phenytoin-resistant kindled rat

Responses to NMDA receptor antagonists altered by epileptogenesis

Löscher W and Hönack D

Trends Pharmacol. Sci., 12, 52, 1991

The first description that kindling-induced epileptic brain changes strikingly increase the adverse effect potential of competitive NMDA receptor antagonists

Anticonvulsant and proconvulsant effects of inhibitors of GABA degradation in the amygdala-kindling model

Löscher W, Jäckel R, and Müller F

Eur. J. Pharmacol., 163, 1–14, 1989

The anticonvulsant effect of vigabatrin correlates with GABA increases in brain nerve endings

Intermittent flumazenil and benzodiazepine tolerance: discouraging findings in rats

Löscher W and Rundfeldt C

Lancet, i, 1386–1387, 1989

The findings indicate that tolerance and physical dependence are distinct properties of benzodiazepines

Is amygdala kindling in rats a model for drug-resistant partial epilepsy?

Löscher W, Jäckel R, and Czuczwar SJ

Exp. Neurol., 93, 211–226, 1986

Description of the first rodent model of pharmacoresistant focal epilepsy

Valproic acid increases γ-aminobutyric acid in CSF of epileptic children

Löscher W and Siemes H

Lancet, ii, 225, 1984

The first clinical demonstration that valproate increases GABA

GABA in plasma and cerebrospinal fluid of different species. Effects of γ-acetylenic GABA, γ-vinyl GABA and sodium valproate

Löscher W

J. Neurochem., 32, 1587–1591, 1979

The first preclinical demonstration that valproate increases GABA in CSF and plasma

Effect of convulsant and anticonvulsant agents on level and metabolism of γ-aminobutyric acid in mouse brain

Löscher W and Frey H-H

Naunyn-Schmiedeberg's Arch. Pharmacol., 296, 263–269, 1977

The first demonstration that valproate counteracts the decrease in GABA synthesis after convulsants

New epilepsy therapies in development

Klein P, Kaminski RM, Koepp M, and Löscher W

Nature Rev. Drug Discov., 23, 682–708, 2024

Of Mice and Men: The Inter-individual Variability of the Brain's Response to Drugs

Löscher W

eNeuro, 11, ENEURO.0518-23.2024, 2024

Epilepsy and epileptiform activity in late-onset Alzheimer disease: clinical and pathophysiological advances, gaps and conundrums

Kamondi A, Grigg-Damberger M, Löscher W, Tanila H, and Horvath AA

Nature Rev. Neurol., 20, 162–182, 2024

The impact of ATP-binding cassette transporters in the diseased brain: Context matters

Baltira C, Aronica E, Elmquist WF, Langer O, Löscher W, Sarkaria JN, Wesseling P, de Gooijer MC, and van Tellingen O

Cell Rep. Med., 5, 101609, 2024

Drug resistance in epilepsy: Clinical impact, potential mechanisms, and new innovative treatment options

Löscher W, Potschka H, Sisodiya SM, and Vezzani A

Pharmacol. Rev., 72, 606–638, 2020

Infections, inflammation and epilepsy

Vezzani A, Fujinami RS, White HS, Preux PM, Blümcke I, Sander JW, and Löscher W

Acta Neuropathol., 131, 211–234, 2016

Re-emergence of neuroinfectiology

Baumgärtner W and Löscher W

Acta Neuropathol., 131, 155–158, 2016

Advances in the development of biomarkers for epilepsy

Pitkänen A, Löscher W, Vezzani A, et al.

Lancet Neurol., 15, 843–856, 2016

New avenues for antiepileptic drug discovery and development

Löscher W, Klitgaard H, Twyman RE, and Schmidt D

Nature Rev. Drug Discov., 12, 757–776, 2013

Perampanel — new promise for refractory epilepsy?

Löscher W and Schmidt D

Nature Rev. Neurol., 8, 661–662, 2012

Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research

Löscher W and Brandt C

Pharmacol. Rev., 62, 668–700, 2010

Drug resistance in brain diseases and the role of drug efflux transporters

Löscher W and Potschka H

Nature Rev. Neurosci., 6, 591–602, 2005

The neurobiology of antiepileptic drugs

Rogawski MA and Löscher W

Nature Rev. Neurosci., 5, 553–564, 2004

The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions

Rogawski MA and Löscher W

Nature Med., 10, 685–692, 2004

The role of the piriform cortex in kindling

Löscher W and Ebert U

Progr. Neurobiol., 50, 427–481, 1996