arbaclofen

Action and Spectrum

Actions and Spectrum: 

arbaclofen, or STX209, is a medication that acts as a selective agonist of GABA-B receptors. It is structurally similar to baclofen but has more excellent selectivity for GABA-B receptors and a longer half-life. 

The main action of arbaclofen is to enhance the activity of GABA-B receptors, which are metabotropic receptors widely distributed throughout the central nervous system. GABA-B receptors have inhibitory effects on neuronal excitability and neurotransmitter release. They are involved in various physiological processes, including learning and memory, motor control, pain modulation, and regulation of mood and anxiety. 

arbaclofen has been investigated for its potential therapeutic effects in several neurological and psychiatric disorders, including autism spectrum disorder, fragile X syndrome, and schizophrenia. However, its clinical efficacy has been variable, and its safety profile is not fully understood. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Sedation/drowsiness 

Hyperactivity 

Lethargy 

Diarrhea 

Weakness 

Agitation 

Headache 

Irritability 

Urinary tract infection (UTI) 

Fatigue 

Dizziness 

Frequent urination 

Insomnia 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

arbaclofen, also known as STX209, is a medication still under investigation, and its use is not yet approved for any indication. However, based on the available information, some contraindications should be considered: 

• Hypersensitivity: arbaclofen should not be used in patients with known hypersensitivity to the medication or its components. 
• Seizures: arbaclofen may lower the seizure threshold and should be used cautiously in patients with a history of seizures or epilepsy. 
• Liver impairment: arbaclofen may be metabolized in the liver, and its use should be avoided or used cautiously in patients with liver impairment. 
• Renal impairment: arbaclofen is primarily excreted in the urine, and its use should be avoided or used with caution in patients with renal impairment. 
• Concomitant use with other medications: arbaclofen may interact with medications that affect the central nervous system or GABAergic neurotransmission, such as benzodiazepines, opioids, and antipsychotics. Therefore, its use should be avoided or used with caution in patients taking these medications. 

Caution 

arbaclofen, also known as STX209, is a medication still under investigation, and its use is not yet approved for any indication. Based on the available information, some cautions should be considered: 

• Pregnancy and breastfeeding: The safety of arbaclofen during pregnancy and breastfeeding has not been established. Therefore, its use should be avoided or used with caution in these populations. 
• Children: The safety and efficacy of arbaclofen in children have not been established. Therefore, its use in pediatric patients should be avoided or used with caution. 
• Elderly patients: Elderly patients may be more susceptible to the adverse effects of arbaclofen, such as sedation and dizziness. Therefore, its use in this population should be avoided or used with caution. 
• Driving and operating machinery: arbaclofen may cause sedation and dizziness, impairing the ability to drive or operate machinery. Therefore, patients should avoid these activities until they know how the medication affects them. 
• Alcohol: arbaclofen may potentiate the sedative effects of alcohol. Therefore, patients should be advised to avoid alcohol while taking this medication. 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy Category: N/A 

Lactation: N/A 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

arbaclofen is a selective gamma-aminobutyric acid type B (GABA-B) receptor agonist. It is believed to work by modulating the activity of GABA-B receptors, which are widely distributed in the central nervous system and play a role in regulating neurotransmitter release, neuronal excitability, and synaptic plasticity. 

Pharmacodynamics: 

Mechanism of action: The action of this substance involves its function as a prodrug, which is converted into the R-enantiomer of baclofen. This enables it to be orally administered with higher bioavailability. 

Pharmacokinetics: 

Absorption 

arbaclofen is rapidly absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours. The bioavailability of arbaclofen is estimated to be around 60-80%. 

Distribution 

arbaclofen is widely distributed throughout the body, including the brain. The volume of distribution of arbaclofen is estimated to be approximately 0.5 L/kg. 

Metabolism 

arbaclofen is primarily metabolized in the liver by cytochrome P450 enzymes, specifically the CYP2C19 and CYP2C9 isoforms. The metabolites are primarily excreted in the urine. 

Elimination and Excretion 

The elimination half-life of arbaclofen is approximately 4-6 hours. Most metabolites are excreted in the urine, with a small portion excreted in the feces. 

Adminstartion

Administration: 

Oral administration 

arbaclofen, also known as STX209, is a medication still under investigation, and its use is not yet approved for any indication. However, based on the available information, here are some general guidelines for its administration: 

• Dosage: The optimal dosage of arbaclofen has yet to be established, and it may vary depending on the indication and the patient’s response to the medication. Dosages ranging from 5-20 mg three times daily have been investigated in clinical trials. 
• Administration: arbaclofen is available in tablet form and should be taken orally with or without food. The tablets should be swallowed whole and not crushed or chewed. 
• Timing: The timing of administration may vary depending on the indication and the patient’s response to the medication. In clinical trials, arbaclofen has been administered up to three times daily. 
• Duration of treatment: The duration of treatment with arbaclofen may vary depending on the indication and the patient’s response to the medication. In clinical trials, treatment durations ranging from several weeks to several months have been investigated. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: arbaclofen 

Why do we use arbaclofen? 

arbaclofen, also known as STX209, is a medication still under investigation, and its use is not yet approved for any indication. However, based on the available information, here are some potential uses of arbaclofen: 

• Fragile X syndrome: arbaclofen is being investigated to treat behavioral symptoms associated with Fragile X syndrome, a genetic disorder that causes intellectual disability, behavioral and emotional problems, and other physical characteristics. 
• Autism spectrum disorder: arbaclofen is being investigated for treating social communication and behavioral symptoms associated with autism spectrum disorder. 
• Spasticity: arbaclofen may effectively reduce muscle spasticity in spinal cord injury, multiple sclerosis, or cerebral palsy patients. 
• Alcohol use disorder: arbaclofen may effectively reduce alcohol consumption and craving in patients with alcohol use disorder. 
• Gastroesophageal reflux disease (GERD): arbaclofen may effectively reduce symptoms associated with GERD, such as heartburn and regurgitation.