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baclofen (Fleqsuvy)

✓ Approved

Azurity Pharmaceuticals, Inc. · GABBR1 · 小分子

什么是 baclofen？

baclofen 是一种小分子，由Azurity Pharmaceuticals, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Fleqsuvy
公司Azurity Pharmaceuticals, Inc.
药物类别小分子
分子靶点GABBR1
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Azurity Pharmaceuticals, Inc.

作用机制

分子靶点

baclofen 作用于 1 个分子靶点：

GABBR1gamma-aminobutyric acid type B receptor subunit 1 (GABABR1, GB1)
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

baclofen 针对 3 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Nervous system disordersMultiple sclerosis✓ Approved
Nervous system disordersMuscle spasticity✓ Approved
Injury, poisoning and procedural complicationsSpinal cord injury✓ Approved

相关研究文献

PubMedFrontiers in rehabilitation sciences2026-10-25

Combined intermittent theta-burst stimulation and functional electrical stimulation as adjuncts to intrathecal baclofen in hereditary spastic paraplegia type 11: a case report.

Zhang Haodong H, Shen Jie J, Qu Yanping Y

Spastic paraplegia type 11 (SPG11) is the most common autosomal recessive subtype of hereditary spastic paraplegia, and is characterized by progressive corticospinal tract degeneration, lower-limb spasticity, and gait impairment. Intrathecal baclofen (ITB) effectively alleviates spasticity, but fails to reverse upstream neural pathway damage, resulting in a "functional ceiling" in motor recovery. Intermittent theta-burst stimulation (iTBS) and functional electrical stimulation (FES) have shown potential for enhancing neuroplasticity; however, their combined use as adjuncts to ITB in SPG11 remains unreported. A 23-year-old female patient with genetically confirmed SPG11 was admitted 2 weeks after ITB pump implantation with severe lower-limb spasticity, an inability to walk independently, and mild anxiety and depression. The patient underwent a 3-month combined intervention comprising iTBS, FES, and conventional rehabilitation, with dynamic interdisciplinary titration of the ITB dosage. Outcomes were assessed using the Modified Ashworth Scale (MAS), Manual Muscle Testing (MMT), the Berg Balance Scale, center of pressure analysis, the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD). After 3 months of intervention, the optimal ITB dose was determined to be 62.82 μg/d. The MAS scores of both legs progressively declined, accompanied by increased MMT grades and improved standing balance. The HAMA and HAMD scores were markedly reduced. No adverse events occurred during the treatment. The combination of iTBS and FES as adjuncts to ITB was associated with improvements in motor function, balance, and psychological status in patients with SPG11. Dynamic interdisciplinary titration of the ITB dose may be important for balancing spasticity control and motor learning.

PMID 42923028
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PubMedTranslational psychiatry2026-10-23

Altered GABAB receptor sensitivity in heavy drinkers indexed using a TMS-based biomarker: a randomized controlled experimental medicine trial.

Montemitro Chiara C, Donahue Daphne D, Costumati Andrea A, Maruottolo Federico F et al.

Metabotropic γ-aminobutyric acid type B receptors (GABABRs) are implicated in alcohol use disorder (AUD) and represent a promising therapeutic target. However, robust biomarkers of GABABRs target engagement and sensitivity in humans are lacking. We examined transcranial magnetic stimulation (TMS)-derived cortical inhibition and growth hormone (GH) release as measures of GABABR function, and whether heavy alcohol use is associated with altered responses to pharmacological GABABR activation. In a randomized, double-blind, placebo-controlled crossover study, 31 healthy volunteers (16 heavy drinkers, 15 light drinkers) received baclofen 30 mg, baclofen 60 mg, or placebo across three sessions. Long-interval intracortical inhibition (LICI), short-interval intracortical inhibition, and intracortical facilitation were assessed with paired-pulse TMS at baseline and ~60 min post-dose. Baclofen blood concentrations and plasma GH levels were measured. Baclofen produced dose-dependent increases in GH release, confirming neuroendocrine GABABR engagement. The LICI response to baclofen differed between groups: In light drinkers, baclofen at 30 mg potentiated LICI, and a similar potentiation was seen at 60 mg, indicating that a plateau may have been reached. In contrast, in heavy drinkers, a potentiation of LICI similar to that in light drinkers was seen at 30 mg baclofen, but was absent at the 60 mg dose despite comparable pharmacokinetics, suggesting altered GABABR function. Effects were selective for GABABR-mediated inhibition, with no consistent modulation of short-interval intracortical inhibition or corticospinal excitability. Acute baclofen administration reveals altered GABABR sensitivity in heavy drinkers, with preserved responses at lower doses but reduced response under stronger agonist stimulation. LICI and GH release provide complementary biomarkers of central and peripheral GABABRs engagement and may support translational development of mechanism-based treatments for AUD.

PMID 42918748
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PubMedPloS one2026-10-16

Concurrent TMS-EEG to characterise interhemispheric signal propagation over the motor and prefrontal regions: An independent replication of GABAB receptor mechanisms.

Zhou Jie J, He Yiting Y, Jin Chenxia C, Yang Chen C et al.

Callosal abnormalities disrupt interhemispheric communications that impair the recovery of a series of neurological and psychiatric disorders. Understanding interhemispheric communication could help identify treatments for disorders with dysfunctional callosal transmission. This study aimed to validate the sensitivity of a TMS-EEG-based measure of interhemispheric signal propagation (ISP) to GABAB receptor modulation, while independently replicating the pharmacological mechanisms of interhemispheric inhibition. A group of 29 participants received an oral dose of either baclofen, a GABAB receptor agonist, or a placebo. Before and after drug intake, single-pulse TMS-EEG was applied to assess ISP in both the motor and prefrontal regions. Our findings indicated that baclofen increased interhemispheric inhibition over the motor region, indexed by significantly decreased ISP (p = 0.037). No significant effect was observed in the dorsolateral prefrontal region (p = 0.186), suggesting regional specificity in GABAB receptor modulation of ISP. These findings uncovered the pharmacological mechanisms of interhemispheric inhibition as indexed by ISP. They also highlight the potential of ISP for characterising interhemispheric communication, which could inform the treatment for a series of disorders with dysfunctional callosal transmission.

PMID 42886653
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PubMedDrug and alcohol dependence2026-10-15

Nationwide trends of six medications for alcohol use disorder prescriptions post-discharge in patients hospitalized with alcohol-associated liver disease between 2015 and 2024.

Chan Shu-Yen SY, Yeo Yee Hui YH, Yang Hsien Yao HY, Zhang Wei W et al.

Alcohol associated liver disease (ALD) carries a high risk of hospitalization and recidivism, yet post-discharge medications for alcohol use disorder (MAUD) are not universally prescribed. MAUD prescriptions have been associated with reduced recidivism and hepatic decompensation. However, national data on prescribing patterns is limited. We examined ten-year trends in six MAUD prescriptions after hospitalization for ALD. We identified 150,241 US adults hospitalized with ALD between 2015 and 2024 using electronic health records from TriNetX. Outcomes included annual prevalence, incidence rate, and incidence proportion of post-discharge MAUD prescriptions. FDA-approved agents included disulfiram, acamprosate, and naltrexone; off-label agents included topiramate, baclofen, and gabapentin. Trends were assessed using Joinpoint regression with annual percentage change (APC) and average annual percentage change (AAPC). Subgroup analyses were stratified by cirrhosis status and sex. FDA-approved MAUD had consistently lower prescription rates than off-label agents over the past decade. From 2015-2024, disulfiram was the only FDA-approved agent with a declining trend, while acamprosate (AAPC 20.35%) and naltrexone (AAPC 17.83%) demonstrated significant increases for new prescriptions. By 2024, the prevalence of FDA-approved and off-label MAUD prescriptions were 17.98% and 41.96%, respectively. Patients with cirrhosis had lower prescribing rates but exhibited greater relative increases in FDA-approved MAUD prescriptions. Women were more likely to receive off-label prescriptions, though both sexes showed similar upward trends. Post-discharge MAUD prescribing for ALD has risen significantly, but less than 20% of patients receive FDA-approved MAUD. Expanding access to evidence-based medications is critical to improve outcomes in this high-risk population.

PMID 42879917
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PubMedTheriogenology2026-10-13

SLC32A1 regulates puberty onset in female mice by modulating GnRH neuron function through Kisspeptin and GABA-GABAB receptor signaling.

Pan Zhihao Z, Zhang Wei W, Han Kejian K, Fu Dongyuan D et al.

This study investigated the role of vesicular γ-aminobutyric acid (GABA) transporter (VGAT/SLC32A1) in initiating puberty in female mice. We first measured the expression of SLC32A1 in the hypothalamic-pituitary-ovary axis of female mice at different developmental stages (infancy, prepuberty, puberty, and adulthood) using real-time quantitative reverse transcription PCR (RT-qPCR) and immunofluorescence. Subsequently, we evaluated the effects of SLC32A1 knockdown on puberty onset in vivo and in vitro, including puberty-related gene expression; proliferation and apoptosis of GT1-7 cells; concentrations of GABA, GnRH, and Kisspeptin; vaginal opening time in female mice; serum concentrations of GABA, progesterone (P4), and estradiol (E2); and ovarian morphology analysis. Finally, we treated Slc32a1 knockdown GT1-7 cells with the GABAB receptor agonist baclofen and assessed changes in puberty-related gene expression and in the concentrations of GnRH, Kisspeptin, and GABA in the culture medium to determine whether SLC32A1 regulates puberty via the GABA-GABAB receptor pathway in vitro. Results revealed that in the hypothalamus of female mice, Slc32a1 mRNA levels declined at puberty, followed by a further decrease in adulthood. In the pituitary, the lowest Slc32a1 mRNA levels were observed during the pubertal and adult stages. In the ovaries, compared with the infant and prepubertal stages, Slc32a1 mRNA levels were significantly reduced in the pubertal and adulthood stages. SLC32A1 was primarily located in the arcuate nucleus (ARC), paraventricular nucleus (PVN) and dorsomedial hypothalamic nucleus (DMH) of the hypothalamus, as well as in the adenohypophysis, the ovarian oocytes and granulosa cells at different developmental stages in female mice. Slc32a1 knockdown in GT1-7 cells increased Gnrh, Gpr54, Igf-1, and Tac2 mRNA expression and cell proliferation, while decreased Sirt1, Gabrb2, and Gabbr1 mRNA levels, and reduced the secretion of GABA, GnRH, and Kisspeptin. Mice with hypothalamic Slc32a1 knockdown exhibited earlier vaginal opening and showed upregulation of Gnrh, Kiss-1, Gpr54, Igf-1, and Tac2 mRNA levels in the hypothalamus, as well as downregulation of Sirt1, Gabrb2, and Gabbr1 mRNA levels; increased Lhβ mRNA in the pituitary; significantly decreased serum GABA levels and significantly elevated serum levels of E2 and P4. In GT1-7 cells, the transcriptional changes in the Gnrh, Gpr54, Igf-1, and Tac2 genes, and Kisspeptin secretion induced by Slc32a1 knockdown were significantly reversed after the addition of baclofen. But it failed to restore the reduced GnRH secretion, it even led to further decreases in GnRH secretion. These findings indicate that SLC32A1 exhibits developmentally dynamic changes along the reproductive axis in female mice, and regulates the function of hypothalamic GnRH neurons; Knockdown of Slc32a1 alters the expression of puberty-related genes in the hypothalamus of female mice, as well as the levels of GABA, E2, and P4 in serum, thereby promoting the onset of puberty. This regulatory effect is partially mediated by the Kisspeptin system through GABAB receptors. This provides novel evidence for the role of SLC32A1 in regulating the onset of puberty.

PMID 42863441
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PubMedJournal of chromatography. A2026-10-09

Cyclization of gabapentinoids as a novel approach for their determination by GC-MS/MS in biological fluids.

Dybowski Michal P MP, Dawidowicz Andrzej L AL, Typek Rafal R, Siwek Krystian K et al.

Gabapentinoids are a group of centrally acting depressant drugs and structural analogues of gamma-aminobutyric acid used to treat neurological disorders. Given their narrow therapeutic window, determining their concentrations in physiological fluids, particularly in human blood plasma, is particularly important for monitoring therapeutic efficacy and ensuring patient safety in routine practice. The results obtained in this study using pregabalin, gabapentin, and baclofen demonstrate that preliminary cyclization is significantly more effective for preparing these gabapentinoids for GC analysis than silylation or methylation. The EDAC/DMTMM mixture was identified as the most suitable catalyst for the cyclization of gabapentinoids. The developed procedure results in complete conversion (near 100%) of the investigated gabapentinoids into their cyclic forms. Importantly, matrix components (i.e. plasma/urine components) do not interfere with the catalyzed cyclization process, and no matrix effect is observed. The proposed method is robust and reproducible (about 98%), and the obtained limits of detection and quantification (lower than 0.9 ng/mL and 3.0 ng/mL, respectively) are comparable to those reported in the literature for standard LC-MS methods and significantly lower than those reported for GC-MS methods involving classical derivatization (silylation or methylation) of these analytes. The applicability of the proposed GC signal-enhancement procedure based on preliminary cyclization was confirmed by the analysis of blood and urine samples containing pregabalin, gabapentin, and baclofen. To the best of our knowledge, this is the first report describing the cyclization of gabapentinoids for their determination in biological fluids by GC; thus, the method represents a novel analytical approach.

PMID 42854462
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