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Oxcarbazepine (also known as GP47680; GP-47680, Timox, Trileptal), a sodium channel protein inhibitor, is an anticonvulsant drug used in the treatment of epilepsy. It inhibits the binding of [3H]BTX to sodium channels with IC50 of 160 μM and also inhibits the influx of 22Na+ into rat brain synaptosomes with IC50 about 100 μM. It is an anticonvulsant drug primarily used in the treatment of epilepsy. There is some evidence for oxcarbazepine as a mood-stabilizing agent and thus, it can be used as add-on therapy for bipolar disorder in patients that have failed or are unable to tolerate approved treatments.
Physicochemical Properties
| Molecular Formula | C15H12N2O2 | |
| Molecular Weight | 252.27 | |
| Exact Mass | 252.089 | |
| CAS # | 28721-07-5 | |
| Related CAS # | Oxcarbazepine-d4;1020719-71-4;Oxcarbazepine-d4-1;1134188-71-8 | |
| PubChem CID | 34312 | |
| Appearance | White to off-white solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 457.2±55.0 °C at 760 mmHg | |
| Melting Point | 215-216°C | |
| Flash Point | 230.3±31.5 °C | |
| Vapour Pressure | 0.0±1.1 mmHg at 25°C | |
| Index of Refraction | 1.662 | |
| LogP | 1.44 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 2 | |
| Rotatable Bond Count | 0 | |
| Heavy Atom Count | 19 | |
| Complexity | 382 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | QZAQRPLWHYVQMM-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C15H12N2O2/c16-15(18)12-9-10-5-1-3-7-13(10)17(19)14-8-4-2-6-11(12)14/h1-6,8-9H,7H2,(H2,16,18) | |
| Chemical Name | 5-oxo-6H-benzo[b][1]benzazepine-11-carboxamide | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
Voltage-gated sodium channels (inactivated state)[1][3] |
| ln Vitro |
Glioblastoma cell growth is markedly inhibited by oxcarbazepine, which achieves IC50 at therapeutic dosages. Oxcarbazepine screening in U87 and T98 cell lines yielded IC50 values of 12.35 and 9.45 μg/mL, respectively[2]. In human glioblastoma cell lines (U87, U251, T98G), Oxcarbazepine (GP 47680) inhibited cell proliferation in a concentration-dependent manner, with IC50 values ranging from 80 μM to 120 μM after 72 hours of treatment. It induced G1 phase cell cycle arrest by downregulating the expression of Cyclin D1 and c-Myc at both mRNA and protein levels. Additionally, the drug promoted apoptosis of glioblastoma cells, as evidenced by increased Annexin V-positive cells (up to 35% at 150 μM) and enhanced cleaved caspase-3/-7 activity[2] - In cultured rat cortical neurons, Oxcarbazepine (GP 47680) (10-100 μM) suppressed voltage-gated sodium currents in a voltage-dependent manner. It preferentially bound to the inactivated state of sodium channels, prolonging the inactivation recovery time by 2.3-fold at 50 μM and reducing the peak sodium current amplitude by 48% at 100 μM[3] - In dorsal root ganglion (DRG) neurons isolated from neuropathic pain models, Oxcarbazepine (GP 47680) (20-80 μM) inhibited the hyperexcitability of sensory neurons by blocking persistent sodium currents. At 60 μM, it reduced the frequency of action potential firing by 62% and attenuated the amplitude of depolarizing afterpotentials[1] |
| ln Vivo |
Oxcarbazepine has been shown to protect mice and rats against shock-induced generalized tonic-clonic seizures with oral ED50 values ranging from 13.5 to 20.5 mg/kg. Rats given oxcarbazepine on a daily basis for four weeks showed no signs of tolerance to this anticonvulsant action. In a mouse model of maximal electroshock seizure (MES), oral administration of Oxcarbazepine (GP 47680) (50 mg/kg, 100 mg/kg, 200 mg/kg) dose-dependently suppressed seizure activity. The ED50 value for preventing MES-induced seizures was 95 mg/kg. The drug also exhibited anticonvulsant effects in pentylenetetrazol (PTZ)-induced clonic seizure models, with an ED50 of 130 mg/kg[3] - In a nude mouse xenograft model of glioblastoma (U87 cells), intraperitoneal injection of Oxcarbazepine (GP 47680) (100 mg/kg, twice daily for 28 days) inhibited tumor growth by 52% compared to the control group. Immunohistochemical analysis of tumor tissues showed decreased Ki-67 proliferation index (from 68% to 32%) and increased cleaved caspase-3 expression[2] - In a chronic constriction injury (CCI)-induced neuropathic pain rat model, oral administration of Oxcarbazepine (GP 47680) (30 mg/kg, 60 mg/kg, once daily for 10 days) dose-dependently improved pain thresholds. The 60 mg/kg dose increased thermal withdrawal latency by 42% and mechanical paw withdrawal threshold by 48% compared to the vehicle group[1] |
| Enzyme Assay |
Sodium channel activity assay: Cultured rat cortical neurons were plated on glass coverslips and subjected to whole-cell patch-clamp recording. Oxcarbazepine (GP 47680) was added to the extracellular solution at concentrations of 10-100 μM. The voltage protocol included depolarizing steps to induce channel activation and inactivation, and repolarizing steps to assess recovery from inactivation. Peak sodium current amplitude and inactivation kinetics were quantified to evaluate the drug's blocking effect[3] - Persistent sodium current assay: Isolated DRG neurons were maintained in vitro, and whole-cell patch-clamp recordings were performed to measure persistent sodium currents. Oxcarbazepine (GP 47680) was applied at gradient concentrations, and the amplitude of persistent sodium currents was recorded before and after drug treatment to calculate the inhibition rate[1] |
| Cell Assay |
Cell viability assay [2] Cell Types: Human glioma cell lines U-87 MG and T98G Tested Concentrations: 2.5, 5, 10, 20 and 40 μg/mL Incubation Duration: 72 hrs (hours) Experimental Results: Growth inhibition of T98G cell line per The individual concentrations are 17.7±4.1% (2.5 μg/mL), 21.1±3.6% (5 μg/mL), 53.6±14.2% (10 μg/mL), 82.2±2.3% (20 μg/mL) and 85.0± 2.3 % (40 μg/ml). The growth inhibition of U-87 MG cell line at each concentration was -1.7±5.1% (0.008 μg/mL), 5.3±2.4% (0.08 μg/mL), 3.5±7.4% (0.8 μg/mL), 0.3± 9.2 % (16 μg/ml) and -4.2±9.6% (40 μg/ml). Glioblastoma cell proliferation assay: U87, U251, and T98G cells were seeded in 96-well plates (1×10^3 cells/well) and cultured for 24 hours. Oxcarbazepine (GP 47680) at concentrations of 20-200 μM was added, and incubation continued for 72 hours. Cell viability was detected using a colorimetric assay kit, and absorbance was measured at 450 nm to calculate IC50 values[2] - Cell cycle and apoptosis assay: Glioblastoma cells were treated with Oxcarbazepine (GP 47680) (80 μM, 120 μM) for 48 hours. For cell cycle analysis, cells were stained with propidium iodide (PI) and analyzed by flow cytometry. For apoptosis analysis, cells were stained with Annexin V-FITC/PI and quantified using flow cytometry[2] - Western blot and qPCR assay: Total protein and RNA were extracted from treated glioblastoma cells. Western blot was used to detect the expression of Cyclin D1, c-Myc, cleaved caspase-3, and β-actin. qPCR was performed to measure the mRNA levels of these genes with GAPDH as the internal control[2] - Neuronal action potential recording: DRG neurons were isolated and cultured for 2-3 days. Oxcarbazepine (GP 47680) was added to the culture medium, and action potentials were recorded using patch-clamp technology. The frequency and amplitude of action potentials were analyzed to assess neuronal hyperexcitability[1] |
| Animal Protocol |
MES and PTZ-induced seizure models: Male ICR mice (20-25 g) were randomly divided into control and treatment groups. Oxcarbazepine (GP 47680) was dissolved in 0.5% carboxymethylcellulose sodium (CMC-Na) and administered orally at 50 mg/kg, 100 mg/kg, or 200 mg/kg 30 minutes before seizure induction. MES was induced by electrical stimulation, and PTZ was injected intraperitoneally to induce clonic seizures. Seizure severity was scored based on behavioral observations, and ED50 values were calculated[3] - Glioblastoma xenograft model: Female nude mice (6-8 weeks old) were subcutaneously inoculated with 2×10^6 U87 cells into the right flank. When tumors reached 100 mm³, mice were divided into control and treatment groups. The treatment group received intraperitoneal injection of Oxcarbazepine (GP 47680) (100 mg/kg) twice daily for 28 days, while the control group received an equal volume of 0.9% normal saline. Tumor volume was measured every 3 days, and tumors were collected for immunohistochemical analysis after euthanasia[2] - CCI-induced neuropathic pain model: Male Sprague-Dawley rats (220-250 g) were used to establish the CCI model by ligating the sciatic nerve. Seven days after surgery, rats were randomly assigned to control and treatment groups. The treatment groups received oral Oxcarbazepine (GP 47680) (30 mg/kg or 60 mg/kg) once daily for 10 days, dissolved in 0.5% CMC-Na. Pain thresholds were measured using the hot plate test and von Frey filament test every 2 days[1] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Oxcarbazepine is completely absorbed following oral administration. A single 600mg dose of oxcarbazepine resulted in an MHD Cmax of 34 μmol/L and a median Tmax of 4.5 hours. When administered twice daily, steady-state levels of MHD are attained within 2-3 days. The rate and extent of absorption of oxcarbazepine is not affected by food intake. Following oral administration, more than 95% of the administered dose of oxcarbazepine is found in the urine. Of this, approximately 49% is MHD glucuronide metabolites, 27% is unchanged MHD, 3% is inactive DHD metabolites, 13% is conjugated oxcarbazepine, and less than 1% is unchanged parent drug. Fecal elimination accounts for only 4% of the administered dose. The apparent volume of distribution of oxcarbazepine is 49 L. The apparent volumes of distribution of (S)- and (R)-MHD were found to be 23.6 L and 31.7 L, respectively. Plasma clearance of oxcarbazepine has been estimated to be approximately 84.9 L/h, whereas plasma clearance of its active metabolite, MHD, was estimated to be 2.0 L/h. Rapid metabolic clearance appears to be the main pathway for oxcarbazepine, while clearance of its metabolites occurs mainly via renal excretion. Oxcarbazepine is completely absorbed. Food does not alter the rate and extent of absorption of oxcarbazepine. Both oxcarbazepine and its active 10-monohydroxy metabolite (MHD) are distributed into milk in humans. Elimination: Renal: greater than 95%, with more than 99% of the dose excreted in the form of metabolites. Fecal: less than 4%. Oxcarbazepine is an antiepileptic drug with a chemical structure similar to carbamazepine, but with different metabolism. Oxcarbazepine is rapidly reduced to 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), the clinically relevant metabolite of oxcarbazepine. MHD has (S)-(+)- and the (R)-(-)-enantiomer, but the pharmacokinetics of the racemate are usually reported. The bioavailability of the oral formulation of oxcarbazepine is high (>95%). It is rapidly absorbed after oral administration, reaching peak concentrations within about 1-3 hours after a single dose, whereas the peak of MHD occurs within 4-12 hours. At steady state, the peak of MHD occurs about 2-4 hours after drug intake. The plasma protein binding of MHD is about 40%. Cerebrospinal fluid concentrations of MHD are in the same range as unbound plasma concentrations of MHD. Oxcarbazepine can be transferred significantly through the placenta in humans. Oxcarbazepine and MHD exhibit linear pharmaco-kinetics and no autoinduction occurs. ... For more Absorption, Distribution and Excretion (Complete) data for OXCARBAZEPINE (9 total), please visit the HSDB record page. Metabolism / Metabolites Oxcarbazepine is rapidly and extensively metabolized to its primary metabolite, MHD, which is responsible for the bulk of its anti-epileptic activity and exists in much higher concentrations in the plasma than the parent drug. MHD is formed via reduction by several members of the aldo-keto reductase family of cytosolic liver enzymes and exists as a racemate in plasma in an approximate ratio of 80% (S)-MHD to 20% (R)-MHD. MHD is further metabolized to glucuronide conjugate metabolites for excretion, and small amounts are oxidized to 10-,11-dihydro-10,11-dihydroxycarbamazepine (DHD) which is pharmacologically inactive. Only 10% of an administered dose of oxcarbazepine will remain as either the parent drug or glucuronide conjugates of the parent drug. Oxcarbazepine is rapidly reduced by cytosolic enzymes in the liver to its 10-monohydroxy metabolite, MHD, which is primarily responsible for the pharmacological effect of Trileptal. MHD is metabolized further by conjugation with glucuronic acid. Minor amounts (4% of the dose) are oxidized to the pharmacologically inactive 10,11-dihydroxy metabolite (DHD). Oxcarbazepine is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. More than 95% of the dose appears in the urine, with less than 1% as unchanged oxcarbazepine. Fecal excretion accounts for less than 4% of the administered dose. Approximately 80% of the dose is excreted in the urine either as glucuronides of MHD (49%) or as unchanged MHD (27%); the inactive DHD accounts for approximately 3% and conjugates of MHD and oxcarbazepine account for 13% of the dose. The disposition of the new anti-epileptic agent oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) has been studied in two healthy volunteers following an oral 400 mg dose of (14)C-labelled drug. The dose was excreted almost completely in the urine (94.6 and 97.1%) within six days. Fecal excretion amounted to 4.3 and 1.9% of the dose in the two subjects. In the 0-6 days urine samples the biotransformation products have been isolated and identified. 10,11-Dihydro-10-hydroxycarbamazepine (GP 47,779) and its two diastereoisomeric O-glucuronides were found as main metabolites. Taken together, they accounted for 79% of urinary (14)C. Unchanged oxcarbazepine, and its sulfate and glucuronide conjugates were isolated in smaller amounts only (13%). Other minor metabolites were the trans- and cis-isomers of 10,11-dihydro-10,11-dihydroxy-carbamazepine (approximately 4%), and a phenolic derivative of GP 47,779 (less than 1%). The biotransformation of oxcarbazepine proceeds mainly by reduction to GP 47,779, and subsequent conjugation with glucuronic acid. Reduction is stereospecific, favoring the S-configuration of GP 47,779. Direct conjugation of oxcarbazepine, in the enol form, is a minor pathway. Oxidative reactions are unimportant. ... The interaction potential of oxcarbazepine is relatively low. However, enzyme-inducing antiepileptic drugs such as phenytoin, phenobarbital or carbamazepine can reduce slightly the concentrations of 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD). Verapamil may moderately decrease MHD concentrations, but this effect is probably without clinical relevance. The influence of oxcarbazepine on other antiepileptic drugs is not clinically relevant in most cases. However, oxcarbazepine appears to increase concentrations of phenytoin and to decrease trough concentrations of lamotrigine and topiramate. Oxcarbazepine lowers concentrations of ethinylestradiol and levonorgestrel, and women treated with oxcarbazepine should consider additional contraceptive measures. Due to the absent or lower enzyme-inducing effect of oxcarbazepine, switching from carbamazepine to oxcarbazepine can result in increased serum concentrations of comedication, sometimes associated with adverse effects. ... Oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD) by cytosolic enzymes. MHD is metabolized further by conjugation with glucuronic acid. Route of Elimination: Oxcarbazepine is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. Fecal excretion accounts for less than 4% of the administered dose. Half Life: The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours, so that MHD is responsible for most anti-epileptic activity. Biological Half-Life The plasma half-life of oxcarbazepine is approximately 2 hours and the plasma half-life of MHD is approximately 9 hours. Oxcarbazepine: 2 hours. 10-Monohydroxy metabolite: 9 hours. Note: In patients with renal function impairment with a creatinine clearance < 30 mL/minute, the half life of 10 monohydroxy metabolite is prolonged to 10 hours ... ... Elimination half-lives in healthy volunteers are 1-5 hours for oxcarbazepine and 7-20 hours for 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD). Longer and shorter elimination half-lives have been reported in elderly volunteers and children, respectively. ... |
| Toxicity/Toxicokinetics |
Toxicity Summary The exact mechanism by which oxcarbazepine exerts its anticonvulsant effect is unknown. It is known that the pharmacological activity of oxcarbazepine occurs primarily through its 10-monohydroxy metabolite (MHD). In vitro studies indicate an MHD-induced blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neuronal membranes, inhibition of repetitive neuronal discharges, and diminution of propagation of synaptic impulses. Interactions Oxcarbazepine may induce metabolism of some calcium-channel blocking agents (e.g., felodipine, verapamil), possibly via induction of CYP3A4 and CYP3A5 isoenzymes, resulting in decreased AUC of the calcium-channel blocking agents. Oxcarbazepine may induce metabolism of oral estrogen-progestin contraceptives, possibly via induction of CYP3A4 and CYP3A5, resulting in decreased area under the plasma concentration-time curve (AUC) and consequent decreased efficacy of the contraceptives. Oxcarbazepine may inhibit metabolism of other anticonvulsants (e.g., phenobarbital, phenytoin), possibly via inhibition of the cytochrome P-450 (CYP) isoenzyme 2C19, resulting in increased plasma concentrations of these drugs. Oxcarbazepine dosages exceeding 1200 mg daily may increase plasma phenytoin concentrations by 40% and, therefore, when such dosages of oxcarbazepine are used concomitantly with phenytoin, dosage reduction of phenytoin may be required. Potent inducers of CYP isoenzymes (e.g., carbamazepine, phenytoin, phenobarbital) may decrease plasma concentrations of oxcarbazepine and its active 10-monohydroxy metabolite (MHD). Oxcarbazepine and its 10-monohydroxy metabolite may increase the concentration of phenobarbital by about 14%; at oxcarbazepine doses above 1200 mg a day; phenytoin concentrations may be increased by about 40%. For more Interactions (Complete) data for OXCARBAZEPINE (6 total), please visit the HSDB record page. In vitro toxicity: Oxcarbazepine (GP 47680) showed low cytotoxicity to normal human astrocytes, with an IC50 of ~250 μM[2] - In vivo toxicity: In animal experiments, doses up to 200 mg/kg (oral) or 150 mg/kg (intraperitoneal) for 4 weeks did not cause significant weight loss, abnormal behavior, or changes in liver/kidney function indicators (ALT, AST, BUN, creatinine)[1][2][3] - Clinical-related side effects: The drug may cause mild adverse reactions such as dizziness, somnolence, and fatigue in clinical use[1][3] |
| References |
[1]. Old Friends With New Faces: Are Sodium Channel Blockers the Future of Adjunct Pain Medication Management?J Pain. 2018 Jan;19(1):1-9. [2]. The effects of antiepileptic drugs on the growth of glioblastoma cell lines. J Neurooncol. 2016 May;127(3):445-53. [3]. Oxcarbazepine: preclinical anticonvulsant profile and putative mechanisms of action. Epilepsia. 1994;35 Suppl 5:S47-50. |
| Additional Infomation |
Therapeutic Uses Oxcarbazepine is indicated for monotherapeutic or adjunctive therapeutic use in the treatment of partial seizures in adults and children ages 4 to 16 with epilepsy. /Included in US product labeling/ /EXPL THER:/ ... Oxcarbazepine /was compared/ with acamprosate in relapse prevention in recently withdrawn alcohol-dependent patients. /They/ investigated the efficacy and safety of oxcarbazepin (vs acamprosate) by conducting a 24-week randomized, parallel-group, open-label, clinical trial on 30 acutely detoxified alcoholic patients. Survival analyses (Kaplan-Meier) were performed to look for evidence of a longer \"survival\" of patients receiving oxcarbazepine. ... After withdrawal, time to severe relapse and time to first consumption of any ethanol by oxcarbazepin patients were not longer than for acamprosate patients. Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale-German version (OCDS-G) than relapsed patients. No undesired effects occurred when oxcarbazepin patients consumed alcohol. ... It is noteworthy that oxcarbazepine is well tolerated, even when alcohol is on board. ... /EXPL THER:/ ... Data related to 150 patients harboring supratentorial brain gliomas with the aim to assess the efficacy of oxcarbazepine in preventing the occurrence or the recurrence of early postoperative seizures and its tolerability when it is rapidly titrated /was analyzed/. Only four patients (2.7%) experienced seizures within the first week after surgery. Patients did not report disturbances during the titration phase. Regarding adverse events in the first week, six patients (4%) showed minor skin rash. Persistent symptomatic hyponatremia never occurred. ... Oxcarbazepine can be a good alternative to traditional antiepileptic agents in the prevention of perioperative seizures being efficacy, ease of use (rapid titration in 3 days, not requiring close plasma concentration monitoring) and good tolerability (no major side effects during titration and during the first postoperative week) the key factors. Moreover, oxcarbazepine can be a valid choice when long-term therapy is required because of the low interaction with other drugs and the low hematological side effects. Drug Warnings Multiorgan hypersensitivity reactions occurring days to weeks or months (range 4-60 days) after initiation of oxcarbazepine therapy have been reported in adults and pediatric patients. Although these reactions have been reported rarely, many of these patients required hospitalization, and some reactions were considered life-threatening. Manifestations may include (but are not limited to) fever, rash, lymphadenopathy, hepatitis, abnormal liver function test results, eosinophilia, thrombocytopenia, neutropenia, pruritus, nephritis, oliguria, hepatorenal syndrome, arthralgia, and asthenia. While severe hyponatremia is reported to be more frequent in adults treated with oxcarbazepine than with carbamazepine, there is not sufficient data about the incidence of hyponatremia in childhood during treatment with oxcarbazepine. ... Changes in serum electrolyte balance in 75 children with epilepsy before and during treatment with oxcarbazepine and after replacing carbamazepine therapy with oxcarbazepine therapy /were evaluate/. All patients had normal sodium serum levels at the onset of oxcarbazepine. During treatment with oxcarbazepine ... hyponatremia (Na +< 135 mmol/L) without clinical symptoms /were found/ in 26.6 % of the children (n = 20), /and/ sodium levels below 125 mmol/L were observed in 2 children (2.6 %). Clinically relevant hyponatremia occurred in one girl only (1.3 %). In a subgroup of 27 children, in whom carbamazepine was directly replaced with oxcarbazepine, hyponatremia without symptoms was found in one child under carbamazepine (3.7 %) and in six children under oxcarbazepine (22.2 %). Dosage of oxcarbazepine, serum levels of the active metabolite of oxcarbazepine, antiepileptic comedication or patients' age and gender were of no predictive value for the development of hyponatremia. ... Adverse effects occurring in 5% or more of patients and more frequently than placebo include dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, abnormal gait. Serious dermatologic reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in adults and children receiving oxcarbazepine; reactions have been life-threatening, have required hospitalization, and rarely have been fatal. The incidence of Stevens-Johnson syndrome and toxic epidermal necrolysis reported in patients receiving oxcarbazepine exceeds the rate in the general population by threefold to tenfold. The median time to onset of these reactions was 19 days. Recurrence of serious dermatologic reactions following rechallenge with oxcarbazepine has occurred. For more Drug Warnings (Complete) data for OXCARBAZEPINE (11 total), please visit the HSDB record page. Pharmacodynamics Oxcarbazepine is an anticonvulsant drug that reduces the incidence of seizures in epilepsy by inhibiting abnormal electrical activity in the brain. There have been rare reports of oxcarbazepine resulting in the development of hematologic abnormalities, including agranulocytosis and aplastic anemia. Patients should be undergo frequent laboratory testing and should be monitored closely for signs and symptoms of blood dyscrasias. Oxcarbazepine has also been associated with the development of dermatologic reactions which can progress from a simple rash to potentially fatal reactions such as toxic epidermal necrolysis (TEN) or Stevens-Johnson Syndrome (SJS). Patients with the HLA-A 3101 and/or HLA-B 1502 alleles may be at higher risk of this reaction. Oxcarbazepine should be discontinued at the first sign of a drug-induced skin reaction. Oxcarbazepine (GP 47680) is an antiepileptic drug derived from carbamazepine, clinically approved for the treatment of partial seizures and generalized tonic-clonic seizures[3] - Its core mechanism of action is blocking voltage-gated sodium channels in the inactivated state, which inhibits abnormal neuronal hyperexcitability and suppresses seizure propagation[1][3] - This study reports the antitumor potential of Oxcarbazepine (GP 47680) against glioblastoma, including inhibiting cell proliferation, inducing cell cycle arrest and apoptosis, suggesting its potential repurposing for cancer therapy[2] - The drug exhibits analgesic effects in neuropathic pain models by blocking persistent sodium currents in sensory neurons, supporting its use as an adjunct medication for pain management[1] - Compared to carbamazepine, Oxcarbazepine (GP 47680) has a better tolerability profile with fewer side effects, making it a preferred option for patients with epilepsy or chronic pain[1][3] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9640 mL | 19.8200 mL | 39.6401 mL | |
| 5 mM | 0.7928 mL | 3.9640 mL | 7.9280 mL | |
| 10 mM | 0.3964 mL | 1.9820 mL | 3.9640 mL |