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topiramate (USL255 / Qudexy XR)

✓ Approved

Upsher-Smith Laboratories, LLC. · GRIA1 · Small Molecule

What is topiramate?

topiramate is a small molecule developed by Upsher-Smith Laboratories, LLC.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesUSL255, Qudexy XR
CompanyUpsher-Smith Laboratories, LLC.
Drug ClassSmall Molecule
Molecular TargetGRIA1, SCN5A
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Upsher-Smith Laboratories, LLC.

Mechanism of Action

Molecular Targets

topiramate acts on 2 molecular targets:

GRIA1glutamate ionotropic receptor AMPA type subunit 1 (GLUR1, HBGR1)
SCN5Asodium voltage-gated channel alpha subunit 5 (CMD1E, SSS1)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

topiramate is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Nervous system disordersPartial seizures✓ Approved
Surgical and medical proceduresMigraine prophylaxis✓ Approved

Related Research Articles

PubMedBMJ case reports2026-07-25

Fenfluramine in refractory SCN1A-related 'genetic epilepsy with febrile seizures plus'.

Takahashi Tatsuya T, Abe Yuichi Y, Hayakawa Itaru I

A child with SCN1A-related 'genetic epilepsy with febrile seizures plus' (GEFS+) presented in infancy with recurrent febrile and afebrile seizures, frequently progressing to generalised tonic-clonic status epilepticus. Despite a severe seizure burden and typical Dravet-like triggers, neurodevelopment remained entirely normal and a familial SCN1A variant supported a diagnosis of GEFS+. The variant (c.5666T>A, p.Met1889Lys) was classified as a variant of uncertain significance fulfilling PM2, PP1 and PP3 criteria and absent from The Genome Aggregation Database (gnomAD) and ClinVar. Identification of the same variant in a neurodevelopmentally normal parent supported inherited GEFS+ rather than Dravet syndrome. After treatment failure with sodium valproate, clobazam and topiramate, low-dose fenfluramine (2.2 mg/day, 0.15 mg/kg/day) achieved seizure freedom maintained for more than 1 year with no adverse effects. This dose is substantially lower than the 0.2-0.7 mg/kg/day used in Dravet syndrome trials, suggesting GEFS+ may require lower therapeutic thresholds.

PMID 42498321
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PubMedThe Lancet. Neurology2026-07-24

Tolerability, safety, and efficacy of atogepant versus topiramate in adults with migraine (TEMPLE): a randomised, head-to-head, phase 3b trial.

Reuter Uwe U, Dycke Annelies Van AV, Versijpt Jan J, Holle-Lee Dagny D et al.

Oral calcitonin gene-related peptide (CGRP) receptor antagonists such as atogepant have been approved for preventive treatment of migraine but have not been compared directly with conventional oral non-specific preventive treatments. Topiramate is a widely used conventional oral non-migraine-specific preventive treatment for migraine but its use is often limited by poor tolerability. We aimed to evaluate the tolerability, safety, and efficacy of atogepant versus topiramate in adults with migraine, to provide direct comparative evidence to help inform treatment selection. TEMPLE was a phase 3b, randomised, double-dummy, active-controlled trial with a 24-week double-blind treatment period and a 52-week open-label treatment period, done in sites with experience in diagnosing and treating migraine across 12 countries (Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Portugal, and the UK). Participants had a history of migraine and at least 4 migraine days per month on average across the 3 months before screening and during the combined screening and baseline period. Participants were randomly assigned 1:1 to atogepant (60 mg once daily) or topiramate (highest tolerated dose of 50 mg/day, 75 mg/day, or 100 mg/day) using interactive response technology. The primary endpoint assessed tolerability by measuring treatment discontinuation owing to treatment-emergent adverse events during the double-blind period in the safety population (all participants who received ≥1 dose of the study treatment during the double-blind period). Secondary efficacy endpoints related to clinical efficacy were at least 50% reduction from baseline in mean monthly migraine days and change from baseline in mean monthly migraine days during months 4-6 in the modified intention-to-treat population (all randomised participants who received ≥1 dose of study treatment, had an evaluable baseline period of eDiary data, and had ≥1 evaluable postbaseline 4-week [1 month] period of eDiary data within 24 weeks after first dose of study medication [month 1 to month 6], regardless of whether on study treatment or off study treatment). TEMPLE is registered with ClinicalTrials.gov (NCT05748483) and EU Clinical Trials Register (2022-501172-25-00); the double-blind period is completed and the open-label period is ongoing. Between Oct 7, 2023, and April 28, 2025, 730 participants were screened, 545 were randomly assigned, and 540 (479 [89%] female and 61 [11%] male, 517 [96%] White) were included in the safety population (atogepant n=273; topiramate n=267). Discontinuation due to treatment-emergent adverse events across the 24-week double-blind period was lower in the atogepant group (33 [12%] of 273) compared with the topiramate group (79 [30%] of 267; relative risk [RR] 0·4, 95% CI 0·3 to 0·6; p<0·0001). Treatment-related adverse events were reported by 153 (56%) of 273 participants in the atogepant group and 208 (78%) of 267 in the topiramate group. Serious treatment-emergent adverse events occurred in six participants on atogepant and in three participants on topiramate. One serious treatment-emergent adverse event (anaphylactic reaction in the atogepant group) was considered related to study drug. No deaths occurred. More participants experienced at least 50% reduction in mean monthly migraine days in the atogepant group (64% [173 of 270]) compared with the topiramate group (39% [101 of 257], RR 1·6, 95% CI 1·4 to 2·0, p<0·0001) and reduction from baseline in mean monthly migraine days was greater in the atogepant group (least squares mean -6·3 [SE 0·3]) than the topiramate group (-4·5 [0·3]; treatment difference -1·8 [-2·5 to -1·0]; p<0·0001). Atogepant 60 mg once daily showed better tolerability and efficacy across 24 weeks compared with topiramate. Although both topiramate and atogepant are established as effective oral migraine preventive treatments, their usefulness in clinical practice hinges on patients' ability to tolerate treatment. Our findings provide direct comparative evidence that might guide clinicians in selecting the most appropriate preventive therapy for their patients. AbbVie.

PMID 42492556
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PubMedThe Enzymes2026-07-23

Challenges and opportunities for developing selective carbonic anhydrase inhibitors and activators for vertebrate isoforms.

Supuran Claudiu T CT

Carbonic anhydrase (CA, EC 4.2.1.1) inhibitors of the sulfonamide/sulfamate type, such as acetazolamide, thiazides/high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, antiepileptics (sulthiame, topiramate, zonisamide), or non-steroidal anti-inflammatory agents such as celecoxib and polmacoxib, are effective inhibitors of most CA isoforms present in vertebrates but their clinical use in various pathologies is associated with side effects. Significant efforts were done in the last decades for developing isoform-selective inhibitors for all 12 catalytically active mammalian isoforms, with important results being obtained by using the tail approach or by the discovery of new inhibitory chemotypes, such as the coumarins and their derivatives, the boron/selenium-containing compounds, etc. SLC-0111, an antitumor sulfonamide in clinical development is an example of a successful strategy emerged by using the tail approach, this compound being a selective inhibitor of the tumor-associated isoforms CA IX and XII. Coumarins, sulfocoumarins and some boron-containing compounds show significant levels of isoform-selective inhibition against many CA isoforms too. Few compounds, on the other hand, show selectivity for inhibiting microbial over vertebrate isoforms, which is a considerable challenge for developing anti-infectives based on CA inhibitors. At the moment, only coumarins act as class-selective inhibitors for α- and η-CAs, not inhibiting significantly other CA classes (β-, γ-, δ-, ζ-, θ- and ι-CAs). Selective CA activators for the mammalian isoforms are not available yet, although they might lead to relevant pharmacological applications for the management of neurodegenerations, emotional memory disorders, obsessive-compulsive disorders, phobias, post-traumatic stress. Finding more effective isoform-selective and more importantly, class-selective modulators of activity for vertebrate CAs might afford opportunities for innovative therapeutic/pharmacological applications.

PMID 42486552
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PubMedThe Enzymes2026-07-23

Carbonic anhydrases I and II.

Supuran Claudiu T CT, Capasso Clemente C

Carbonic anhydrase (CA, EC 4.2.1.1) isoforms I (CA I) and II (CA II) are widespread cytosolic proteins in most vertebrates. They are abundant in the red blood cells and many other tissues, being involved in physiological processes such as pH regulation, CO₂/bicarbonate homeostasis, respiration, and secretion of electrolytes rich in acid or bicarbonate in the stomach, kidneys, cerebrospinal fluid, eyes, and bones. The genetics, biochemistry, expression, localization in tissues and organs, kinetic properties, and catalytic mechanisms of these enzymes are well understood at the molecular level. At least five different inhibition mechanisms were described with more than 50 chemotypes acting as inhibitors. The activation with amine/amino acid activators was also well studied. The physiological role of CA I is poorly understood, whereas CA II is a physiologically dominant isoform, playing crucial functions in a host of tissues/organs. Interfering with its activity by means of inhibitors has been and is currently exploited in therapy for the management of edema, glaucoma, epilepsy, obesity, acute mountain sickness, and idiopathic intracranial hypertension. Promising preclinical data pointed to the potential use of CA II inhibitors for the management of other conditions, such as neuropathic pain, cerebral ischemia, rheumatoid arthritis, Alzheimer's disease, osteoporosis, and obstructive sleep apnea. Many CA inhibitors are in clinical use for the management of such conditions, among which are acetazolamide, thiazides and high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, and antiepileptics such as sulthiame, topiramate and zonisamide, whereas SLC-0111 is in clinical development as an antitumor agent. CA activators are not yet used clinically, but they might have pharmacological applications in the management of neurodegeneration, emotional memory disorders, obsessive-compulsive disorders, phobias, generalized anxiety, and post-traumatic stress. Finding novel modulators of activity for these enzymes may lead to innovative therapeutic applications and deepen our understanding of enzymes, their inhibitors, and their activators.

PMID 42486551
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PubMedAnnals of the American Thoracic Society2026-07-21

Respiratory Adverse Events of Weight-Loss Drugs: A Systematic Review and Meta-Analysis.

Zeng Lijuan L, Zinmon-Htet Celeste C, Hundie Tsegaye T, Lin Shanshan S et al.

The coexistence of obesity and asthma is increasingly common and associated with poorer asthma outcomes. Weight loss has been shown to improve asthma outcomes. Although several effective weight-loss medications are available, evidence regarding their respiratory effects remains limited. To conduct a systematic review of the respiratory adverse events (AEs) associated with weight-loss medications in general populations and specifically among individuals with asthma. We searched Medline, Embase, Cochrane, and CINAHL, as well as trial registries, without date or language restrictions. We included randomized controlled trials, nonrandomized comparative studies, and large, single-group studies assessing the respiratory AEs of liraglutide, semaglutide, tirzepatide, orlistat, naltrexone-bupropion, phentermine-topiramate, and setmelanotide. We assessed the risk of bias in each study using design-specific, validated tools. We conducted random-effects model-based meta-analyses of risk differences for respiratory AEs, comparing active interventions and placebo. Our searches yielded 9,086 unique records. We included 123 studies, of which 122 studies evaluated general populations and one study specifically evaluated individuals with asthma. Overall, the randomized trials had low risk of bias. Liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion were not associated with increased respiratory AEs compared with placebo. Insufficient data limited comparisons for other drugs. Respiratory events, such as upper respiratory tract infections and nasopharyngitis, were common, with nasopharyngitis incidence ranging from 4.1% (95% CI: 0.7%, 9.3%; tirzepatide, 0-6 months) to over 23.7% (95% CI: 19.6%, 28.1%; liraglutide, 13-24 months), although these were not clearly associated with doses or indications. Evidence specifically addressing individuals with asthma was sparse. There was no evidence of increased respiratory harm associated with weight-loss drugs compared with placebo, suggesting a reassuring respiratory safety profile in the general population. However, evidence specifically focused on individuals with asthma remains limited.

PMID 42479131
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PubMedEpilepsy research2026-07-19

Neuropsychiatric adverse events with anti-seizure medications in patients with epilepsy: A systematic review and meta-analysis.

Kumar Kunal K, Roy Sweta S, Kaushal Himanshu H, Muanda Flory T FT et al.

Anti-seizure medications (ASMs) are the cornerstone of epilepsy pharmacotherapy; however, emerging evidence suggests a potential link between ASM use and neuropsychiatric adverse events (NPAEs). We aimed to synthesise observational evidence on the risk of NPAEs with ASM use in patients with epilepsy. Medline, Embase, and PsycINFO were searched from inception to May 2026. Primary outcomes included the occurrence of behavioural, cognitive, mood, sleep, and psychotic disorders with ASM use compared with control groups in patients with epilepsy. Where studies were sufficiently comparable, risk ratios were pooled with 95% confidence intervals using a random-effects model; otherwise, findings were summarized narratively. Of 6769 retrieved citations, 18 observational studies including 5151,367 patients were identified. Memory disorders were reported in 8.7%, 3.8%, and 6.2% of participants receiving first-, second-, and third-generation ASMs, respectively. Depression was reported in 2.3%, 1.2%, and 3.0%, respectively. No statistically significant difference in psychosis risk was observed between first- and second-generation ASMs (RR 0.77; 95% CI 0.34-1.76). Second-generation ASMs had a lower point estimate for psychotic disorders compared with third-generation ASMs, but this finding was borderline and imprecise, with the unrounded confidence interval crossing the null value. Topiramate demonstrated the strongest association with psychosis risk (OR 3.07; 95% CI 2.55-3.71), and levetiracetam was notably associated with higher rates of anxiety in one cohort and higher odds of suicidality in one nested case-control study. ASM use in patients with epilepsy is accompanied by a range of NPAEs, with risk varying across distinct types of ASMs. These findings support considering NPAEs in ASM selection and routine monitoring in patients with epilepsy. The observational nature of the included studies, residual confounding, heterogeneity in comparator groups, outcome definitions, and limited data on dose, duration, polytherapy, and newer ASMs limit the precision and generalizability of findings.

PMID 42470751
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