baclofen (Xylka / Baclocur / baclofen, Ethypharm)

Scalp Acupuncture Combined with Exercise Induces PI3K/Akt Activation and Improves Synaptic Plasticity in Post-Stroke Spastic Rats.

Zhao Sainan S, Li Lingxu L, Li Wenna W, Wang Chunmeng C et al.

Effective treatments for post-stroke spasticity (PSS) remain limited, and the mechanism by which scalp acupuncture combined with exercise (SAE) alleviates PSS is not fully understood. This study investigated the effects of SAE in rats with PSS and explored whether SAE regulates synaptic plasticity through the PI3K/Akt pathway. A middle cerebral artery occlusion (MCAO) rat model was established, and rats were randomly assigned to five groups: Blank, Sham, MCAO, SAE, and Baclofen. All interventions were administered for 7 consecutive days. Neurological function, cerebral infarct volume, histopathology, synaptic ultrastructure, and related protein expression were then evaluated. Compared with the MCAO group, SAE improved neurological deficits, reduced muscle hypertonia, decreased infarct volume, alleviated neuronal injury, increased synapse number, and improved synaptic morphology. SAE also upregulated glial cell line-derived neurotrophic factor (GDNF), phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-AKT), and synaptic proteins, including synaptophysin (SYN), postsynaptic density protein 95 (PSD-95), and growth-associated protein 43 (GAP-43). Immunofluorescence staining further suggested enhanced expression of SYN and p-Akt in the motor cortex after SAE treatment. These findings suggest that SAE may be correlated with the activation of PI3K/Akt signaling via upregulation of GDNF, thereby improving synaptic plasticity and alleviating PSS symptoms. This study investigated the effects of SAE in rats with PSS and explored the potential association between SAE intervention, PI3K/Akt pathway activity, and synaptic plasticity.

[Comparison of the side effect profiles of compounds with central muscle-relaxing effect].

Kopitkó Csaba C, Pettendi Éva É

In addition to other conditions involving increased muscle spasms, centrally acting muscle relaxants (guaifenesin, tolperisone, methocarbamol, chlorzoxazone, diazepam, baclofen and tizanidin) provide relief for a significant proportion of patients suffering from low back pain. Of these, tolperisone has recently been restricted by official decision due to the high incidence of anaphylactic reactions associated with its use. The aim of our work is to analyze the frequency of side effects of this group of drugs in order to help clinicians choose the appropriate medication. According to data from the World Health Organization, tolperisone is considered a safe drug, except for the aforementioned serious allergic side effect. Mortality (including suicide) associated with the administration of these medicines is the highest among the reported side effects for diazepam, followed by tizanidine and methocarbamol. Ineffectiveness was most commonly reported for guaifenesin, followed by baclofen and tizanidine. Tolperisone was the most favorable drug in terms of both mortality and ineffectiveness. We present in detail the gastrointestinal, major neurological, and psychiatric side effects that make it difficult, and in some cases impossible, to take the drugs, and we also mention the disturbing skin and eye symptoms. Orv Hetil. 2026; 167(31): 1224-1230.

[The debate on baclofen deserves better than trials by suspicion].

Rolland Benjamin B, Karila Laurent L, Franchitto Nicolas N, Barrault Camille C et al.

Personalized Drug Repurposing Screen Identifies Patient-Specific Therapeutic Candidates for Mucopolysaccharidosis Type IIIB.

McDaniel Kathleen D KD, Ghousifam Neda N, Bowling Rodney A RA, Chen Catherine Z CZ et al.

Background: Mucopolysaccharidosis type IIIB (MPSIIIB, Sanfilippo syndrome type B) is a rare lysosomal storage disease caused by deficiency of alpha-N-acetylglucosaminidase (NAGLU) enzyme, leading to progressive accumulation of heparan sulfate and severe neurological decline. MPSIIIB's significant genetic heterogeneity presents a major barrier to developing broadly effective treatments and suggests a need for personalized therapeutic strategies. Methods: We established a personalized drug repurposing platform using high-content imaging with lysotracker dye as an indirect functional readout of lysosomal dysfunction to screen compounds that correct lysosomal defects in patient-derived fibroblasts. We screened 2807 compounds on cells from an MPSIIIB patient with a homozygous NAGLU p.Arg297Ter mutation. Hits that reduced lysosomal accumulation by at least 25% with minimal cytotoxicity were validated and subsequently tested for efficacy in fibroblasts from a second patient with a different, compound heterozygous NAGLU genotype. Results: The primary screen yielded 72 hits (2.6% hit rate), with 10 confirmed in dose-response assays. Notably, four clinically approved drugs-baclofen, dextrose, epalrestat and moxifloxacin-reduced lysosomal accumulation in the index patient's cells. However, none of these four drugs were effective in the second patient's cells, demonstrating a profound patient-specific effect. Only one non-clinical compound, 6-chlorothymol, showed a trend toward activity in both cell lines. Conclusions: Our study demonstrates a feasible framework for conducting rapid, N-of-1 drug repurposing screens for rare diseases. While we identified four promising candidates for the index patient, the lack of efficacy in a second patient cell line underscores that genetic heterogeneity may preclude a "one-size-fits-all" approach for MPSIIIB. These findings support the integration of individualized drug screening as a potential precision-medicine strategy, offering a potential path toward patient-specific therapies for rare diseases rather than traditional drug development.