metaxalone / Generic mfg. - LARVOL DELTA

Assess the Effect of Metaxalone 640 mg (M640) Compared to Tizanidine 8 mg on Truck Driving Ability and Cognition (clinicaltrials.gov) - P4 | N=20 | Completed | Sponsor: Primus Pharmaceuticals | Trial primary completion date: May 2024 ➔ Dec 2024

Trial primary completion date • Alzheimer's Disease • Cognitive Disorders

PMMSS-01: Efficacy of M640 in Acute Lumbosacral Musculoskeletal Conditions. (clinicaltrials.gov) - P4 | N=50 | Active, not recruiting | Sponsor: Primus Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain

Study to Assess Drowsiness, Cognition, Fall Risk After Metaxalone 640 mg and Metaxalone 800 mg (clinicaltrials.gov) - P4 | N=20 | Completed | Sponsor: Primus Pharmaceuticals | Recruiting ➔ Completed | Trial completion date: Mar 2025 ➔ Oct 2024 | Trial primary completion date: Mar 2025 ➔ Sep 2024

Trial completion • Trial completion date • Trial primary completion date

Assess the Effect of Metaxalone 640 mg (M640) Compared to Tizanidine 8 mg on Truck Driving Ability and Cognition (clinicaltrials.gov) - P4 | N=20 | Completed | Sponsor: Primus Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Alzheimer's Disease • Cognitive Disorders

Manubrial-Sternal Joint Injection for Refractory Tietze Syndrome (ASA 2024) - "She had failed conservative therapies: > 6 weeks of physical therapy, NSAIDs, lidocaine patch, diclofenac cream, TENS unit, duloxetine, pregabalin, and metaxalone. Physical examination revealed + TTP at the sternoclavicular joint, and thoracic MRI ruled out radicular pain. Under fluoroscopic and ultrasound guidance, a manubrial-sternal joint injection (dexamethasone and bupivacaine) was performed, successfully resolving pain and making corticosteroid injection a viable therapeutic alternative for refractory Tietze Syndrome."

Immunology • Pain

Pain Control After Lumbar Spine Fusion (clinicaltrials.gov) - P4 | N=428 | Enrolling by invitation | Sponsor: Rothman Institute Orthopaedics

New P4 trial • Pain

Dehydroxylative radical N-glycosylation of heterocycles with 1-hydroxycarbohydrates enabled by copper metallaphotoredox catalysis. (PubMed, Nat Commun) - "The synthetic utility is showcased through the late-stage functionalization of bioactive compounds and pharmaceuticals like Olaparib, Axitinib, and Metaxalone. Mechanistic studies prove the presence of glycosyl radicals and the importance of copper metallaphotoredox catalysis."

Journal

Effect of Metaxalone 640 mg (M640) on Truck Driving Ability and Cognition Compared to Other Skeletal Muscle Relaxants (clinicaltrials.gov) - P4 | N=20 | Recruiting | Sponsor: Primus Pharmaceuticals

New P4 trial • Alzheimer's Disease • Cognitive Disorders

Study to Assess Drowsiness, Cognition, Fall Risk After Metaxalone 640 mg and Metaxalone 800 mg (clinicaltrials.gov) - P4 | N=20 | Recruiting | Sponsor: Primus Pharmaceuticals

New P4 trial

Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations. (PubMed, J Pain Res) - "From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer's disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future."

Journal • Review • Addiction (Opioid and Alcohol) • Alzheimer's Disease • CNS Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Oncology • Pain • CYP2C19

Comparative Risk of Injury with Concurrent Use of Opioids and Skeletal Muscle Relaxants. (PubMed, Clin Pharmacol Ther) - "In the oxycodone-SMR-triggered cohort, the adjusted hazard ratios (HRs) were 1.86 (95% CI, 1.23-2.82) for carisoprodol and 1.73 (1.09-2.73) for tizanidine. In the tramadol-synchronically triggered cohort, the adjusted HRs were 0.69 (0.49-0.97) for metaxalone and 0.62 (0.42-0.90) for tizanidine. In the tramadol-SMR-triggered cohort, the adjusted HRs were 1.51 (1.01-2.26) for baclofen and 1.48 (1.03-2.11) for cyclobenzaprine...In conclusion, the relative injury rate associated with different SMRs used concurrently with the three most dispensed opioids appears to vary depending on the specific opioid and the order of combination initiation. If confirmed by future studies, clinicians should consider the varying injury rates when prescribing SMRs to individuals using hydrocodone, oxycodone, and tramadol."

Journal

Genome-wide study reveals novel roles for formin-2 in axon regeneration as a microtubule dynamics regulator and therapeutic target for nerve repair. (PubMed, Neuron) - "In silico screening of FDA-approved drugs identified metaxalone, administered either immediately or 24-h post-injury, accelerating function recovery. This work uncovers a novel axon regeneration function of Fmn2 and a small-molecule strategy for PNI."

Journal • HDAC5

Effacacy of M640 in Acute Lumbosacral Musculoskeletal Conditions. (clinicaltrials.gov) - P4 | N=50 | Recruiting | Sponsor: Primus Pharmaceuticals

New P4 trial • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain

Metabolic activation and cytotoxicity of metaxalone mediated by cytochrome P450 enzymes and sulfotransferases. (PubMed, Chem Biol Interact) - "Both methoxsalen (MTS, a CYP2A6 inhibitor) and 2,6-dichloro-4-nitrophenol (DCNP, a sulfotransferase inhibitor) dramatically decreased the formation of M2. Pre-treatment of primary hepatocytes with DCNP or MTS significantly decreased the susceptibility to the cytotoxicity of MTX."

Journal • Hepatology • Inflammation • Musculoskeletal Pain • Pain

Biocatalytic Synthesis of Metaxalone and Its Analogues. (PubMed, Org Lett) - "Gram-scale synthesis of chiral and racemic metaxalone was achieved with 44% (98% ee) and 81% yields, respectively, by protein engineering of the halohydrin dehalogenase HHDHamb from Acidimicrobiia bacterium. Additionally, various metaxalone analogues were synthesized at 28-40% yields (90-99% ee) for chiral forms and 77-92% yields for racemic forms."

Journal

Regioselective C-H Thiocyanation of Arenes by Iron(III) Chloride Catalysis. (PubMed, J Org Chem) - "Iron(III) chloride was found to be an effective Lewis acid for the activation of N-thiocyanatosaccharin and the subsequent thiocyanation of a wide range of activated arenes. The procedure was applicable for the thiocyanation of biologically active compounds such as metaxalone and an estradiol derivative and was used as part of a one-pot tandem iron-catalytic process for the regioselective, dual functionalization of an arene building block."

Journal

Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants. (PubMed, Medicina (Kaunas)) - "Time-varying confounder-adjusted IRRs ranged from 0.31 (95% confidence interval: 0.13-0.77) for metaxalone to 3.44 (95% confidence interval: 1.53-7.78) for tizanidine. We identified a potential >3-fold increase in the rate of hospitalized thromboembolism in concomitant users of warfarin + tizanidine vs. warfarin alone. Alternative explanations for this finding include confounding by indication, a native effect of tizanidine, or chance."

Journal • Cardiovascular

Comparative Risk of Opioid Overdose With Concomitant use of Prescription Opioids and Skeletal Muscle Relaxants. (PubMed, Neurology) - "Concomitant use of prescription opioids and baclofen relative to cyclobenzaprine is associated with opioid overdose. Clinical interventions may focus on prescribing alternatives in the same drug class or providing access to opioid antagonists if treatment with both medications is necessary for pain management."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Infectious Disease • Pain • Septic Shock • Substance Abuse

Articulating target-mining techniques to disinter Alzheimer's specific targets for drug repurposing. (PubMed, Comput Methods Programs Biomed) - "This virtual analysis forecasted the repurposable potential of Ziprasidone, Melfoquine and Metaxalone against AD based on their affinity towards RGS4, a key AD-specific target."

Journal • Alzheimer's Disease • CNS Disorders • Retinal Disorders • RGS4

Isostructural cocrystals of metaxalone with improved dissolution characteristics. (PubMed, RSC Adv) - "The absence of stronger heterosynthons between MET and the coformers, their lower melting points and the high solubility of the coformers are the probable reasons for the enhanced solubility of the bioactive component. The MET-NAM cocrystal exhibited the highest solubility/dissolution rate among the three binary solid forms, which may offer improved bioavailability and a lower dose with minimal side effects."

Journal • Pain

Demonstration of relative bioavailability of newly developed and innovator drug metaxalone 800 mg in healthy subjects under fed condition. (PubMed, J Adv Pharm Technol Res) - "The assessment product is analogous to reference product in relation to degree and extent of absorption. The outcome of this study indicates the newly developed drug is equivalent to the innovator drug and medication was well tolerated by all participants."

Journal

The Relative Efficacy of Seven Skeletal Muscle Relaxants. An Analysis of Data From Randomized Studies. (PubMed, J Emerg Med) - "Among patients in the ED with acute LBP treated with a nonsteroidal anti-inflammatory drug, SMRs do not improve outcomes more than placebo. Neither age, sex, nor baseline impairment impacts these results."

Journal • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells. (PubMed, Int J Mol Sci) - "Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-α, and IL-6, enhanced IL-13, and also increased PPARγ, PGC-1α, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation."

Journal • CNS Disorders • Immunology • Inflammation • Oncology • IL13 • IL1B • IL6 • NFE2L2 • TNFA

Utilization patterns of skeletal muscle relaxants among commercially insured adults in the United States from 2006 to 2018. (PubMed, Pain Med) - "SMRs are widely used in the United States. Their use slightly increased in recent years but trends varied among individual agents, patient groups, and geographic regions. Despite limited evidence to support efficacy, a sizable number of U.S. adults used SMRs for long-term and off-label conditions. Further study is needed to understand determinants of treatment as well as outcomes associated with such use."

Clinical • Journal • Musculoskeletal Diseases • Musculoskeletal Pain • Pain

Formulation, validation and evaluation studies on metaxalone and diclofenac potassium topical gel. (PubMed, Environ Anal Health Toxicol) - "Batch F7 emerged as the best batch on the basis of favourable pH, high drug content, homogeneity and drug release. HPLC (High-performance liquid chromatography) method validation of gel formulation was also carried out and the developed and validated method was found to be robust and accurate."

Journal • Immunology • Inflammation • Pain