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sumatriptan succinate (Zelrix / NP101 / Zecuity)

✓ Approved

Nupathe Inc. · HTR1D · Small Molecule

What is sumatriptan succinate?

sumatriptan succinate is a small molecule developed by Nupathe Inc.. It is approved for therapeutic indications via topical or transdermal.

Drug Profile

Brand NamesZelrix, NP101, Zecuity
CompanyNupathe Inc.
Drug ClassSmall Molecule
Molecular TargetHTR1D
RouteTopical, Transdermal
StatusApproved
Sources: ClinicalTrials.gov, Nupathe Inc.

Mechanism of Action

Molecular Targets

sumatriptan succinate acts on 1 molecular target:

HTR1D5-hydroxytryptamine receptor 1D (HTR1DA, HT1DA)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

sumatriptan succinate is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Nervous system disordersMigraine✓ Approved

Related Research Articles

PubMedFrontiers in endocrinology2026-09-19

Increased HIF-2α and CD105 (endoglin) expression is associated with poor differentiation in pheochromocytomas and paragangliomas.

Günler Tuğba T, Çordan İlker İ

Reliable biomarkers reflecting tumor biology and histopathological risk status in pheochromocytomas and paragangliomas (PPGL) remain limited. In this study, the expression of biomarkers associated with hypoxia, angiogenesis, and proliferation was evaluated, and their associations with histopathological differentiation in PPGL were investigated. A total of 35 tumor foci from 31 patients with PPGL who were surgically treated were retrospectively examined. Expression levels of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor (VEGF), CD105 (endoglin), Ki-67, and succinate dehydrogenase subunit B (SDHB) were assessed using immunohistochemical methods. Associations between these markers and clinicopathological characteristics, Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) scores were analyzed. HIF-2α expression, CD105 microvessel density (MVD) score, and Ki-67 proliferation index were significantly higher in poorly differentiated tumors compared with moderately/well-differentiated tumors (p<0.05 for all). In contrast, VEGF expression did not differ significantly between the groups. The GAPP score showed positive correlations with HIF-2α (r=0.48; p<0.01), CD105 (r=0.54; p<0.001), and Ki-67 (r=0.77; p<0.001). In univariate analyses, bilateral disease, HIF-2α expression, CD105 MVD score, and loss of SDHB expression were associated with higher GAPP scores. However, in multivariable regression analysis, only CD105 was independently associated with the GAPP score (β=0.04; p=0.026). Increased expression of CD105, HIF-2α, and Ki-67 was associated with poorer histopathological differentiation in PPGL. Among the biomarkers evaluated, only CD105 showed an independent association with the GAPP score, suggesting that tumor-associated neoangiogenesis may contribute to histopathological differentiation in PPGL. These findings support further investigation of CD105 as a potential biomarker for histopathological risk assessment. However, larger studies with long-term clinical outcome data are needed to establish its clinical prognostic value.

PMID 42760995
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PubMedEndocrine-related cancer2026-09-18

Investigating the clinical utility of plasma succinate with insights from a Sdhb deficient murine model.

Cole Yasemin Y, Abramovich Ifat I, Fernandez-Garcia Jonatan J, Docquier France F et al.

The succinate dehydrogenase (SDH) enzyme composed of four subunits (A-D) has a key role in the Krebs cycle and oxidative phosphorylation. Germline pathogenic variants (GPV) in the genes encoding the four subunits of the succinate dehydrogenase (SDH) enzyme (SDHA/SDHB/SDHC/SDHD), collectively known as SDHx are recognized as a paradigm for the role of disordered metabolism in oncogenesis as GPVs in SDHx lead to a truncated citric acid cycle due to reduced or absent function of the SDH enzyme and accumulation of the oncometabolite succinate. GPVs in SDHx are the most common cause of hereditary PPGL and are associated with a higher risk of malignant PPGL and predispose to other tumors including renal cell carcinoma, gastrointestinal stromal tumors (GIST) and pituitary adenomas. Utilizing the linkage of SDHx to metabolic dysfunction, we performed prospective plasma metabolomics and identified succinate as a biomarker for early diagnosis of an underlying SDHx variant. Succinate reflected SDHx deficiency, in individuals with germline predisposition and a small number of patients with somatic SDHx deficiency, and succinate levels correlated with tumor burden. Longitudinal sampling of patients illustrated that serial succinate measurements might be used as a biomarker for disease surveillance. These findings were validated by tissue analysis in a mouse model of Sdhb deficiency, where elevated succinate was observed in adrenal glands. While circulating plasma levels did not mirror the human cohort, this discrepancy suggests specific cellular thresholds for succinate or SDHx deficiency in adrenal gland tissue and highlights species-specific metabolic regulation.

PMID 42758527
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PubMedMetabolism: clinical and experimental2026-09-18

SDHB deficiency promotes renal fibrosis by triggering mtRNA leakage and activating the RIG-I-MAVS pathway.

Zhu Zijing Z, Chen Ping P, Shu Hongxin H, Zeng Qinglin Q et al.

While mutations in tricarboxylic acid (TCA) cycle enzyme succinate dehydrogenase B (SDHB) are well-established drivers of renal cell carcinoma via the accumulation of the oncometabolite succinate, its precise role in renal fibrosis remains entirely unexplored. In this study, we demonstrate that SDHB is down-regulated in fibrotic kidneys. Tubule-specific knockdown of Sdhb exacerbated fibrosis, mitochondrial dysfunction, and inflammation in unilateral ureteral obstruction (UUO) mice, while its overexpression exerted protective effects. Mechanistically, SDHB deficiency induced succinate accumulation, which directly bound to residue Leu150 (L150) of voltage-dependent anion channel 1 (VDAC1), promoting VDAC1 oligomerization and triggering mitochondrial RNA (mtRNA) leakage. Cytosolic mtRNA activated the retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) pathway, driving proinflammatory responses. Pharmacological inhibition of VDAC1 oligomerization by VBIT-4 attenuated mtRNA release. Furthermore, we identified E2F transcription factor 4 (E2F4) as an upstream transcriptional activator of SDHB, and overexpression of E2f4 restored SDHB expression and ameliorated renal pathology. These findings provide mechanistic insights into how TCA cycle disruptions and mtRNA leakage interactions drive renal inflammation, suggesting SDHB as a potential therapeutic target for renal fibrosis.

PMID 42759926
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PubMedFrontiers in microbiology2026-09-18

Fluopyram in agricultural ecosystems: environmental fate, microbial transformation, ecotoxicity, and resistance risks of an SDHI fungicide.

Zhang Chaoqun C, Ullah Muhammad Zafar MZ, Guan Chengwei C, Mubeen Mustansar M et al.

Fluopyram is a next-generation succinate dehydrogenase inhibitor (SDHI) fungicide, which is very popular in the management of economically significant fungal conditions in cereals, fruits, vegetables, and ornamental crops. It works by inhibiting the complex II present in the mitochondria by blocking succinate dehydrogenase, which electron transport and energy generation, eventually hindering fungal development leading to death of the pathogen. Besides having good fungicidal effects, fluopyram has also demonstrated a nematicidal effect, which has also enhanced its utility in various agricultural systems. Empirical studies indicate that SDHIs can induce mortality, mitochondrial dysfunction, oxidative stress, and developmental delays in non-target organisms. Additionally, the environmental persistence of these compounds raises concerns about their potential for ecological disruption. The extensive and growing use of SDHIs however has also given rise to the issue of resistance development with recorded resistance cases in a number of fungal populations and has placed a strong demand on the need to use crop rotation strategies, combination formulations and resistance monitoring initiatives. In addition to its agronomic advantages, the environmental fate of fluopyram such as its mobility, persistence and degradation characteristics in soil and water and the possibility of food system residues have been the subject of attention. Unlike previous studies focusing on isolated aspects, this review comprehensively links efficacy, environmental dynamics, and mechanistic toxicity of fluopyram across multiple biological systems. It highlights underexplored areas including metabolite toxicity, chronic ecological exposure, and resistance risks. This integrated approach offers valuable insights for safer pesticide management and future research directions.

PMID 42756409
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PubMedExperimental neurology2026-09-17

Intermittent theta-burst stimulation in ischemic stroke: a mitochondria-centered framework connecting microglial reprogramming and neuronal survival.

Liu Yue Y, Zhang Yizhuo Y, Huang Yingying Y, Bi Xia X

Ischemic stroke triggers a mitochondrial metabolic crisis that propagates secondary injury through neuroimmune and neuron-intrinsic mechanisms. Within minutes, collapse of oxidative phosphorylation (OXPHOS) drives succinate accumulation; upon reperfusion, rapid succinate re-oxidation generates a burst of mitochondrial reactive oxygen species (ROS) via reverse electron transport, triggering neuroinflammation, blood-brain barrier disruption, and regulated neuronal death. Intermittent theta burst stimulation (iTBS), a time-efficient repetitive transcranial magnetic stimulation protocol, targets this crisis at a systems level. Preclinical evidence indicates that iTBS restores neurovascular integrity, reprograms microglial activation by suppressing the succinate/hypoxia-inducible factor-1α (HIF-1α)-driven Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/ NLR family pyrin domain-containing 3 (NLRP3) inflammasome cascade, and promotes a reparative immune microenvironment. We further propose that restoration of microglial OXPHOS may couple inflammatory resolution to enhanced synthesis of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), forming a metabolic bridge between immune resolution and neuronal survival-a connection assembled from independently supported components but not yet tested as an integrated pathway in the iTBS context. At the neuron-intrinsic level, iTBS suppresses apoptosis via miR-34c-5p/p53/Bax signaling, attenuates ferroptosis by restoring iron homeostasis and antioxidant capacity, and reinforces mitochondrial quality control through transcription factor EB (TFEB)-mediated autophagy. We propose a mitochondria-centered framework wherein mitochondrial homeostasis serves as the central integrative hub linking microglial immunometabolic reprogramming to neuron-intrinsic survival programs. This framework is intended as a hypothesis-generating synthesis rather than a summary of established causal pathways; several of its central links, including the microglial succinate-itaconate axis and the OXPHOS-trophic bridge, remain to be tested directly in iTBS-treated tissue. Preliminary clinical studies report functional improvements across motor, cognitive, language, and swallowing domains, although sample sizes are limited and protocols heterogeneous. We discuss translational challenges including parameter heterogeneity, and note that peripheral markers such as plasma succinate and cell-free mitochondrial DNA warrant exploration as candidate pharmacodynamic indices rather than as a validated response-guided panel.

PMID 42753899
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PubMedRedox biology2026-09-17

Resistance to atrial fibrillation domestication and mitochondrial dysfunction in sheep: a potential key role of the TCA cycle and mitochondrial redox state.

Caluori Guido G, Nattel Stanley S, Pinson Benoît B, Naud Patrice P et al.

Atrial fibrillation (AF) often progresses from paroxysmal to more stable forms. It is well-recognized that patients vary in their AF progression, but the underlying mechanisms remain unclear. This work, performed in a sheep AF-model, aimed to identify atrial redox and energetic status differences between animals developing stable AF (AF-S) versus those resistant to AF-stabilization (AF-R). AF was induced with bursts of atrial tachystimulation, maintained whenever sinus rhythm resumed, and monitored with telemetry. Electrophysiological and structural remodeling were assessed via contact mapping, and histology, respectively. Proteomic, metabolomic, enzymatic, and bioenergetic remodeling were evaluated using left atrial appendage (LAA) tissues and isolated LAA mitochondria. Healthy rats were used to investigate whether a metabolic challenge stabilizes electrically induced AF episodes. AF-S (N = 12) sheep developed stable AF after 13 days on average, whereas AF-R (N = 8) sheep failed to develop self-sustained AF despite 120 days of tachypacing. Contact mapping and histological analysis revealed that AF-S animals presented reduced atrial conduction velocity, and increased endomysial fibrosis. Metabolic analysis showed significant differences in tricarboxylic acid cycle (TCA) enzymes activities and a 45% succinate content increase in AF-S LAA versus AF-R. AF-S mitochondria showed abnormal succinate oxidation, decreased ATP synthesis rate, and increased ROS emission. The ratios of ATP/ADP, NAD+/NADH, and Complex I/II activities were disturbed in AF-S compared to AF-R. Calculated mitochondrial NAD+/NADH ratios suggest an oxidized state in AF-S while AF-R showed a reduced state. Exogenous succinate was metabolized when incubated with rat atrial cardiomyocytes, while intravenous succinate injection stabilized atrial arrhythmias electrically-induced in vivo. AF-S sheep showed TCA cycle, energetic and redox adaptations compared to AF-R. In this animal model, TCA cycle remodeling and associated redox and energetic responses determined the resistance to AF domestication, with potential relevance to identify new mechanistic determinants of AF progression in humans.

PMID 42753315
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