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cocaine hydrochloride (Numbrino)

✓ Approved

Lannett · SCN5A · 小分子

什么是 cocaine hydrochloride?

cocaine hydrochloride 是一种小分子,由Lannett研发。该药已获批,用于治疗相关适应症,给药途径:Topical。

药物档案

商品名Numbrino
公司Lannett
药物类别小分子
分子靶点SCN5A
给药途径Topical
状态Approved

作用机制

分子靶点

cocaine hydrochloride 作用于 1 个分子靶点:

SCN5Asodium voltage-gated channel alpha subunit 5 (CMD1E, SSS1)
需要更深入的分析?Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

cocaine hydrochloride 针对 2 个适应症,涉及 1 个治疗领域。

治疗领域疾病/病症分期
Nervous system disordersAnaesthesia✓ Approved
Nervous system disordersSensory loss✓ Approved

相关研究文献

PubMedForensic science, medicine, and pathology2026-07-27

Cerebrospinal fluid as a post-mortem toxicological matrix: qualitative reliability and quantitative limitations in a cocaine-positive cases.

Crudele Graziano Domenico Luigi GDL, Franceschetti Lorenzo L, Cecalupo Lorenza L, Amadasi Alberto A et al.

Background in forensic toxicology, the detection of pharmacologically active exogenous substances is routinely performed. Interpretation of analyte concentrations must consider multiple variables, markedly affected by diffusion and degradation. These factors complicate toxicological assessment and have stimulated interest in alternative substrates. To assess the toxicological informativeness of cerebrospinal fluid (CSF) through comparison with standard post-mortem matrices, and to investigate whether quantitative relationships exist between CSF and femoral blood concentrations of cocaine and benzoylecgonine. CSF and standard toxicological matrices were collected from 10 forensic cases and three controls. All specimens underwent solid-phase extraction followed by HPLC-Orbitrap mass spectrometry for detection and quantification of cocaine, benzoylecgonine, and other relevant substances. Cocaine and benzoylecgonine were consistently detected in cerebrospinal fluid whenever present in standard matrices, indicating their passage across the blood-brain barrier and supporting CSF as a reliable alternative post-mortem matrix. However, the limited sample size and absence of temporal or clinical information precluded robust quantitative interpretation, highlighting the need for larger studies to clarify pharmacokinetic relationships. Cocaine and benzoylecgonine are detectable in cerebrospinal fluid when present in peripheral blood, but no stable proportional relationship allowing quantitative extrapolation from CSF to femoral blood could be established.

PMID 42507270
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PubMedClinical toxicology (Philadelphia, Pa.)2026-07-27

Acute cardiovascular complications of sympathomimetic recreational drug use.

Gresnigt Femke M J FMJ

Recreational drug use is rising globally, with significant cardiovascular implications. Sympathomimetic substances such as cocaine, amfetamine(amphetamine)-type stimulants and synthetic cathinones are increasingly associated with emergency department presentations and acute cardiac events. Despite this growing burden, standardized guidance for diagnosing and managing acute sympathomimetic recreational drug-related cardiovascular complications remains limited. A narrative review of the literature was conducted to identify acute cardiovascular complications associated with commonly used recreational drugs. A PubMed search was performed from database inception to 1 March 2024 using combinations of cardiovascular symptoms and cardiovascular complications with terms related to sympathomimetic recreational drug use. These substances exert potent sympathomimetic effects through catecholamine excess, and cause receptor activation, ion channel interference, and direct myocardial toxicity. Cocaine additionally induces vasospasm and thrombosis via endothelin-1 and causes sodium channel and potassium channel blockade. Amfetamine-type stimulants and synthetic cathinones amplify catecholamine release, contributing to arrhythmia, ischemia, and myocardial injury. Acute cardiovascular manifestations include chest pain, acute coronary syndrome, arrhythmias, cardiomyopathy, and sudden cardiac death. Presentations often mimic classical cardiac syndromes but may be more severe, especially in younger patients without traditional risk factors. Diagnosis begins with detailed history-taking, although self-reported drug use is frequently unreliable. Depending on symptoms, electrocardiography, cardiac biomarkers and echocardiography may be essential for risk stratification and identifying the underlying pathology. Toxicological testing may be considered when clinically indicated and should be interpreted in conjunction with clinical findings. For cocaine associated chest pain patients, risk stratification with the HEART pathway may guide safe discharge in low-risk cases. Management should be individualized based on the specific recreational drug involved and the presenting symptoms. Sedation, antihypertensives, and dual antiplatelet therapy are foundational, with vasodilators when indicated. Beta-blockers with alpha-blocking properties may be beneficial in selected patients. Early drug counselling and referral are critical to reduce recurrence. In most cases, evaluation and management of acute cardiovascular symptoms in patients with suspected sympathomimetic drug use should follow standard guideline-based cardiovascular care. However, specific modifications may be required, including selective use of toxicological testing when it is expected to influence clinical decision-making, early sedation to reduce sympathetic overactivity, and cautious selection of beta-blockers depending on the substance involved. Awareness of these distinctions is essential to avoid both under- and overtreatment. Clinicians must recognize the acute cardiovascular risks of sympathomimetic recreational drugs and integrate routine drug screening, tailored management, and addiction intervention into acute care pathways to improve outcomes and reduce morbidity.

PMID 42504704
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PubMedOrganic letters2026-07-27

Divergent Access to Chiral Pyrrolidinone-Fused 4H-Pyrans and Pyridines Via Organocatalytic Asymmetric Decarboxylative Addition-Annulation of β-Keto Acids with 2,3-Dioxopyrrolidines.

Li Tianxing T, He Tianyu T, Meng Weiyue W, Jin Hui H et al.

We disclose an unprecedented organocatalytic asymmetric decarboxylative Michael addition of β-keto acids to 2,3-dioxopyrrolidines, enabling the efficient assembly of chiral pyrrolidinone-fused [3,4-b]-4H-pyrans and [3,4-b]-pyridines. The reaction affords chiral pyrrolidinone-tethered 1,5-dicarbonyl intermediates in high yields with excellent regio- and enantioselectivities. Acid-promoted intramolecular cyclization of these adducts provides enantioenriched pyrrolidinone-fused [3,4-b]-4H-pyrans without erosion of enantiopurity, whereas cyclocondensation with hydroxylamine hydrochloride delivers diverse pyrrolidinone-fused [3,4-b]-pyridines. Notably, this protocol is compatible with a one-pot tandem process and gram-scale synthesis.

PMID 42504541
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PubMedToxins2026-07-27

Enhanced Protection Against Toxicity of Nemopilema nomurai Venom Using a PEG-EGCG/Tetracycline Hydrochloride Micellar Nanocomplex.

Li Jie J, Hu Yanan Y, Qian Yunfeng Y, Luo Sai S et al.

Jellyfish stings are the most common type of marine life injuries. However, at present, the treatment measures against jellyfish stings are mostly empirical and supportive, with uncertain therapeutic outcomes, and there is a lack of specific antidotes based on the toxic mechanism of jellyfish venom in clinical practice. In our previous study, polyphenol epigallocatechin-3-gallate (EGCG) was found to neutralize the toxicity of jellyfish Nemopilema nomurai venom (NnV) in vivo and in vitro. Herein we further demonstrated that EGCG exerted its antagonistic effect against NnV through inhibiting the oxidative stress, pro-apoptotic proteins, and systemic inflammatory responses. Subsequently, we constructed a polyethylene glycol (PEG)-EGCG/tetracycline hydrochloride (HTC) co-loaded micellar nanocomplex in order to enhance the stability and bioavailability of EGCG in vivo, which successfully integrated the membrane-repair function of PEG, the enzyme inhibitory effect of HTC and the antioxidant properties of EGCG. Notably, this micellar nanocomplex demonstrated significant protective effects against both functional damage and pathological alterations in a non-lethal NnV-envenomed mouse model. When administered 1 h after NnV envenomation, EGCG (40 mg/kg), HTC and PEG-EGCG (containing 40 mg/kg EGCG) only partially improved abnormal blood biochemical indicators and moderately alleviated histopathologic damage, and PEG-EGCG/HTC containing merely 8 mg/kg EGCG completely mitigated the toxic reactions in envenomed mice. In the preventive regimen, the administration of EGCG, HTC or PEG-EGCG 30 min before exposure showed no significant improvement in abnormal blood biochemical indicators and histopathologic damage, while PEG-EGCG/HTC could still significantly improve the functional impairments and histopathologic damage of the heart and liver in NnV-envenomed mice. These findings suggest the clinical translational potential of PEG-EGCG/HTC against jellyfish envenomation.

PMID 42506698
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PubMedMedical sciences (Basel, Switzerland)2026-07-27

The Gut Microbiota in Addiction Biology: A Systematic Review of Substance-Induced Dysbiosis and Gut-Brain Axis Alterations.

Esparza-Sánchez Juan J, Garibi-Miranda Diego Alejandro DA, Chávez-Tinoco Marco M, Mejía-Méndez Jorge L JL et al.

Growing evidence suggests that chronic substance use disrupts the gut microbiota composition and function, which can contribute to intestinal dysfunction, systemic inflammation, and gut-brain axis dysregulation. However, current evidence remains fragmented and heterogenous, with most studies focusing on individual substances rather than substance-specific microbial signatures. Therefore, this systematic review synthesizes recent evidence (2019-2025) to characterize the impact of chronic substance use, including alcohol, nicotine, opioids, cocaine, and methamphetamine, on the gut microbiota composition and functional integrity. Following the PRISMA 2020 guidelines, a total of 91,421 records were identified before screening through searches conducted across electronic databases and publisher platforms, including PubMed, Web of Science, ProQuest, and BSCOhost, among others. After duplication removal and application of the predefined eligibility criteria, 60 studies were selected for qualitative analysis. The findings revealed an interspecies similarity in which chronic substance exposure generally induced dysbiosis characterized by a depletion of beneficial short-chain fatty acid (SCFA)-producing taxa, such as Lactobacillus, Akkermansia, and Faecalibacterium, alongside the enrichment of opportunistic pathogens such as Escherichia-Shigella. Alcohol emerged as a particularly potent ecological driver, consistently reducing the richness and diversity of the microbial community. Mechanistically, these alterations are linked to impaired intestinal barrier function, increased lipopolysaccharide translocation, and the activation of systemic inflammatory pathways. Furthermore, substance-specific metabolic fingerprints were identified, including disruptions in glutamate pathways for cocaine and trimethylamine N-oxide precursors for methamphetamine. Preclinical evidence from fecal microbiota transplantation and germ-free models suggests that these microbial shifts actively modulate reward sensitivity and neuroplasticity through the gut-brain axis. Collectively, the data presented in this study support a shift from reductionist addiction models toward a systems-level framework, positioning the gut microbiome as a pivotal, modifiable component of addiction biology and a promising target for novel therapeutic interventions.

PMID 42506336
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PubMedAnalytical methods : advancing methods and applications2026-07-27

Smartphone-based fluorescence sensing platform for tetracycline determination based on a high quantum yield europium metal-organic framework with a dual-ligand strategy.

Cheng Shuang S, Song Jintian J, Wen Yue Y, Xu Yijia Y et al.

Ultrasensitive and visual detection of tetracyclines (TCs) is of great significance to public health and environmental safety. Herein, we synthesized a dual-ligand europium metal-organic framework (Eu-phen-MOF) via a one-step solvothermal method for the fluorescence detection of TCs. Compared with the Eu-MOF without 1,10-phenanthroline, Eu-phen-MOF exhibits superior stability, lower LOD and higher quantum yield. It delivers superior TC sensing performance and anti-interference, enabling high-accuracy detection with limits of 152.0 nmol L-1, 249.4 nmol L-1, 171.0 nmol L-1 and 277.7 nmol L-1 for tetracycline (TC), oxytetracycline (OTC), doxycycline hydrochloride (DOX), and chlortetracycline (CTC), respectively. Eu-phen-MOF was used for the quantitative detection of TC, OTC, DOX, and CTC in real samples (milk, eggs, and river water) and recoveries ranging from 94.64% to 105.37% were achieved. Finally, a portable fluorescence sensing platform integrating a smartphone and the Eu-phen-MOF fluorescent hydrogel was constructed, enabling convenient, rapid, and low-cost detection of TCs. This work not only highlights the significance of the dual-ligand strategy for fabricating an efficient TC sensor, but also develops a rapid and visual method for TC detection.

PMID 42504902
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