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metoclopramide (Gimoti / EVK 001 / EVK001)

✓ Approved

Evoke Pharma, Inc. · DRD2 · Small Molecule

What is metoclopramide?

metoclopramide is a small molecule developed by Evoke Pharma, Inc.. It is approved for therapeutic indications via inhaled or intranasal or oral (po).

Drug Profile

Brand NamesGimoti, EVK 001, EVK001
CompanyEvoke Pharma, Inc.
Drug ClassSmall Molecule
Molecular TargetDRD2, HTR4, PTGS1, PTGS2
RouteInhaled, Intranasal, Oral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Evoke Pharma, Inc.

Mechanism of Action

Molecular Targets

metoclopramide acts on 4 molecular targets:

DRD2dopamine receptor D2 (D2R, D2DR)
HTR45-hydroxytryptamine receptor 4 (5-HT4R, 5-HT4)
PTGS1prostaglandin-endoperoxide synthase 1 (PHS1, PGHS-1)
PTGS2prostaglandin-endoperoxide synthase 2 (COX2, COX-2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

metoclopramide is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Gastrointestinal disordersGastric atony✓ Approved

Related Research Articles

PubMedInternational journal of pharmaceutics2026-08-30

Intranasal delivery of Semaglutide using a thermoresponsive PNPHO nanocarrier: formulation development, characterization and biological evaluation.

Sayka Khan Tanisha Tabassum TT, Jerry Wong Chun Yuen CY, Sheikh Zara Z, Fathi Ali A et al.

Semaglutide (SMG) is a glucagon-like peptide-1 receptor agonist with a promising efficacy and safety profile that is widely used for reducing obesity by targeting the appetite control centres in the brain and for type 2 diabetes management by enhancing insulin release and suppressing glucagon secretion. SMG is currently administered subcutaneously that is invasive with reduced patient compliance or orally leading to decreased efficacy owing to first-pass effects. In this study, a nanoparticle (NP) formulation of SMG was developed using a thermoresponsive and biocompatible synthetic polymer, PNPHO (poly(N-isopropylacrylamide-co-(N-acryloxysuccinimide)-co-(polylactide/-hydroxy methacrylate)-co-(oligo (ethylene glycol)), to investigate its potential to enhance nasal mucosal absorption and prolong residence time via the needle-free intranasal (IN) route. The NP formulation was characterized in vitro for physicochemical parameters, stability, mucoadhesion, regional nasal deposition, drug release profile, and cellular permeation, and in vivo for glucose sensitivity and biodistribution. Monodispersed NPs displayed an average size of 26.14 ± 0.19 nm, a negative surface charge with high SMG encapsulation (89%), improved stability against enzymatic degradation and increased permeation across nasal epithelial cells in vitro compared to SMG alone (p < 0.0001). In contrast, it reduced transport across hCMEC/D3 BBB cells. Nasal cast studies revealed greater NP deposition in the turbinates compared to the free drug. In vivo, the NP formulation demonstrated prolonged nasal retention of the formulation within the sinus region along with an improved glucose tolerance with a 24 h dosing regimen, showing an extended period of pharmacological activity that can be utilized for reducing dosing frequency. No detectable brain fluorescence was observed in vivo. Overall, these findings corroborate the potential of IN delivery of thermoresponsive SMG-PNPHO NP formulation with increased efficacy compared to current SMG delivery modes.

PMID 42669320
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PubMedExpert opinion on drug delivery2026-08-30

Lpb. plantarum inhalation powders for the reduction of lung inflammation and S. aureus growth control in non-CF bronchiectasis.

Glieca Stefania S, Tambassi Martina M, Schianchi Chiara C, Quarta Eride E et al.

The reduced diversity of the lung microbiome in respiratory conditions, including bronchiectasis, promotes bacterial infection and inflammation, contributing to worsening clinical outcomes. Traditional treatments often fail to address both infection and inflammation. Because of their potential dual-action, lactic acid bacteria (LAB) directly administered to the lungs could represent an innovative therapeutic approach for these diseases. Two powders for inhalation containing Lpb. plantarum, lactose, l-leucine with and without raffinose, a prebiotic, were produced by spray drying and in vitro tested. The focus was on investigating their potential in vitro anti-inflammatory and anti-microbial activities against S. aureus. The powders showed a fine particle fraction (<5 µm) >40% and allowed to maintain anti-inflammatory activity in vitro for both treatment and prevention. Moreover, both the powders led to a significant reduction in S. aureus growth. The stability study of the powders in capsules at different storage conditions showed the preservation of the LAB up to 90 days in refrigerated conditions (4°C/-20°C). This proof-of-concept study shows that inhalable spray-dried live LABs retain biological activity and are suitable for pulmonary delivery, supporting their potential as a microbiota-modulating therapy which, however, requires further preclinical validation.

PMID 42669029
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PubMedMaterials today. Bio2026-08-30

Intranasal L-DOPA/TPP-engineered extracellular vesicles deliver icariin to ameliorate mitochondrial dysfunction with associated sphingolipid remodeling in Alzheimer's disease models.

Wu Beibei B, Wu Junyong J, Zhu Lemei L, Li An A et al.

Alzheimer's disease (AD) is associated with mitochondrial dysfunction, oxidative stress, and disrupted lipid homeostasis, but the therapeutic translation of mitochondrial-protective agents remains limited by inefficient brain delivery, insufficient neuronal selectivity, and poor subcellular precision. Here, we developed an intranasal extracellular vesicle formulation (L-DOPA/TPP-EV-ICA) by loading icariin (ICA) into mesenchymal stem cell-derived extracellular vesicles and post-inserting DSPE-PEG-Levodopa and TPP-PEG-PE to enhance nasal environment, neuronal association, and mitochondria-associated intracellular enrichment. The engineered vesicles retained EV-like morphology, showed measurable ICA encapsulation, and maintained colloidal stability under the tested storage and simulated nasal conditions. In a human nasal epithelial Transwell model, L-DOPA/TPP-EV-ICA showed greater neuronal uptake than unmodified EVs without detectable disruption of epithelial barrier integrity and exhibited preferential colocalization with mitochondria-associated structures after cellular internalization. In Aβ-injured neuronal cells, L-DOPA/TPP-EV-ICA treatment reduced mitochondrial oxidative stress and mPTP opening, improved membrane potential, and enhanced ATP production and redox-related parameters. Following intranasal administration, the engineered formulation generated stronger and more persistent brain-associated fluorescence and showed preferential association with NeuN-positive cells. In APP/PS1 mice, treatment improved cognitive performance, and attenuated histopathological and mitochondrial abnormalities. Integrated proteomic, metabolomic analyses, and protein-level analyses further identified treatment-associated alterations in sphingolipid-related pathways. These findings support L-DOPA/TPP-EV-ICA as a promising preclinical intranasal EV platform for improving mitochondrial function and modulating sphingolipid-associated alterations in AD-related models.

PMID 42668476
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PubMedRespirology case reports2026-08-30

Use of High-Flow Nasal Cannula in Amyotrophic Lateral Sclerosis Patients Intolerant to Non-Invasive Ventilation: A Case Series.

Varon-Vega Fabio F, Franco Parra Carlos Evelio CE, Adame Ochoa Doris Fabiola DF, Uricoechea Nancy N et al.

Non-invasive ventilation (NIV) is standard respiratory support for amyotrophic lateral sclerosis (ALS), but intolerance may limit its use. High-flow nasal cannula (HFNC) has emerged as a potential alternative in selected patients, but evidence regarding its use remains scarce. We describe 18 ALS patients' management with HFNC between 2014 and 2024 after documented intolerance to NIV. Mean age at HFNC initiation was 65.1 ± 12.5 years, and 66.7% of patients were female. Partial NIV intolerance occurred in 38.9% of cases, while 33.3% tolerated intermittent combined NIV and HFNC. During follow-up, 50.0% of patients required hospitalization, 33.3% experienced respiratory infections, and 27.8% died. Arterial blood gas parameters remained stable, including PaCO2 (p = 0.314). Functional status declined significantly, with Barthel Index decreasing (35.0 ± 20.5 vs. 11.7 ± 11.3; p < 0.001), whereas respiratory muscle strength remained unchanged. HFNC was feasible as home-based support in ALS patients intolerant to NIV, warranting prospective comparative evaluation.

PMID 42668676
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PubMedThe journal of allergy and clinical immunology. Global2026-08-30

ALOX15-driven ω-6 fatty acid metabolism promotes type 2 inflammation in eosinophilic chronic rhinosinusitis with nasal polyps.

Sakashita Masafumi M, Kidoguchi Masanori M, Imoto Yoshimasa Y, Sato Yohei Y et al.

Local lipid metabolism contributes to immune homeostasis in the nasal mucosa and the pathogenesis of chronic rhinosinusitis. However, lipid mediator networks underlying eosinophilic chronic rhinosinusitis (ECRS) remain poorly defined. To characterize fatty acid-derived lipid mediator profiles in nasal polyps (NPs) from patients with and without ECRS and identify pathways associated with eosinophilic inflammation. Lipidomic profiling was performed using LC-MS/MS on NP tissues from patients with ECRS (n = 4) and without ECRS (n = 4). A total of 158 ω-6 and ω-3 fatty acid-derived lipid mediators were quantified. Arachidonate 15-lipoxygenase (ALOX15) pathway activity was evaluated by quantitative PCR and ELISA. ECRS NPs displayed a distinct lipidomic signature compared with non-ECRS NPs. ECRS NPs exhibited increased levels of proinflammatory ω-6 fatty acid metabolites, including 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid, along with elevated ALOX15 pathway products and higher ALOX15 mRNA expression. Anti-inflammatory specialized proresolving mediators, such as lipoxin A4, were also elevated within the ω-6 pathway, and lipoxin A4 levels correlated with 15-HETE levels. These patterns indicate the concurrent activation of pro- and anti-inflammatory pathways, with a predominance of ALOX15-driven ω-6 metabolites in ECRS. In contrast, the ω-3 fatty acid pathway showed only modest increases in 14,15-DiHETE and resolvin D2, suggesting a limited compensatory resolution response compared with the robust ALOX15-dependent ω-6 activity. ECRS NPs exhibit a skewed lipid mediator profile characterized by enhanced ALOX15-dependent ω-6 metabolism and insufficient resolution activity. This imbalance may underlie persistent type 2 inflammation in ECRS and suggests that targeting the 15-lipoxygenase pathway may offer therapeutic benefits.

PMID 42668469
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PubMedPhotodiagnosis and photodynamic therapy2026-08-30

Choroidal microvascular heterogeneity across non-autoimmune type 2 diabetes mellitus subtypes defined by beta-cell function and insulin resistance: a wide-field Swept-Source OCTA study.

Wu Xiaoyan X, Li Qiong Q, Cui Yi Y, Xu Nuo N

To investigate the intergroup differences in choroidal thickness (CT), choroidal vascularity index (CVI), and choroidal vascular volume (CVV) across non-autoimmune type 2 diabetes mellitus (T2DM) subtypes defined by beta-cell function and insulin resistance. This cross-sectional study enrolled 22 healthy controls (22 eyes) and 85 T2DM patients (85 eyes). T2DM patients were categorized into 4 groups using K-means clustering: Severe Insulin-deficient Diabetes (SIDD) =22, Severe Insulin-resistant Diabetes (SIRD)=26, Mild Obesity-related Diabetes (MOD)=16, and Mild Age-related Diabetes (MARD)=21. CT, CVI, CVV were measured by widefield swept-source optical coherence tomography angiography (WSS-OCTA) across three concentric annular regions(0 - 10 mm, 10 - 15 mm, and 15 - 20 mm), subdivided into 12 sectors. Linear mixed-effects and multivariate regression models were constructed to evaluate intergroup differences. Compared with the control group, both CT and CVV decreased significantly in most of the 12 analyzed regions across all T2DM groups, whereas the MOD and SIRD groups exhibited no statistically significant global changes. In contrast, CVI exhibited pronounced spatial and subtype-specific heterogeneity. In the SIDD group, CVI decreased in most regions, with significant reductions in the nasal sector of the 0 - 10 mm annulus (P<0.01]), and in the nasal and inferior sectors of the 10 - 15 mm annulus (P<0.01] and -0.065 (P<0.01). Conversely, the SIRD group demonstrated a widespread increase in CVI, with significant increased in the nasal (P < 0.05), superior (P < 0.05), and temporal (P < 0.05]) sectors of the 15 - 20 mm annulus. Compared with CT and CVV, CVI shows the highest spatial heterogeneity. This indicates that divergent metabolic drivers may exert opposing effects on choroidal vascular remodeling. This subtype-specific characterization enhances our understanding of diabetic choroidopathy pathophysiology and holds potential for guiding personalized screening and therapeutic strategies.

PMID 42669328
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