Mechanism of Action of Oxcarbazepine (Trileptal)
Oxcarbazepine primarily works by blocking voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminished propagation of synaptic impulses. 1
Primary Mechanism
Oxcarbazepine itself is a prodrug that is rapidly metabolized in the liver to its pharmacologically active 10-monohydroxy metabolite (MHD), which is responsible for most of the drug's therapeutic effects:
Voltage-gated sodium channel blockade: The primary mechanism involves:
- Stabilization of hyperexcited neural membranes
- Inhibition of repetitive neuronal firing
- Reduction in synaptic impulse propagation 1
Secondary mechanisms that contribute to anticonvulsant effects:
- Increased potassium conductance
- Modulation of high-voltage activated calcium channels 1
Pharmacokinetics
Understanding the pharmacokinetic profile helps explain how oxcarbazepine exerts its effects:
Metabolism: Oxcarbazepine undergoes rapid reduction by cytosolic enzymes in the liver to form MHD 1, 2
- Only 2% of plasma radioactivity is due to unchanged oxcarbazepine
- Approximately 70% is present as MHD
- Half-life of parent compound: ~2 hours
- Half-life of MHD: ~9 hours
Absorption: Complete absorption with median tmax of 4.5 hours (range 3-13 hours) 1
- Steady-state plasma concentrations reached within 2-3 days
- Linear pharmacokinetics at doses of 300-2,400 mg/day
- Food has no effect on absorption
Differences from Carbamazepine
Despite structural similarities to carbamazepine, oxcarbazepine has distinct pharmacological properties:
Metabolic pathway: Unlike carbamazepine which is oxidized by cytochrome P-450 system, oxcarbazepine undergoes reductive metabolism at its keto moiety 3
- Minimal involvement of hepatic cytochrome P-450-dependent enzymes
- Lower potential for drug-drug interactions compared to carbamazepine
Calcium channel effects: Oxcarbazepine modulates different types of calcium channels compared to carbamazepine 3
CNS effects: Oxcarbazepine induces fewer alterations in saccadic and smooth-pursuit eye movements compared to carbamazepine, suggesting potentially fewer CNS side effects 4
Clinical Applications
The mechanism of action explains oxcarbazepine's effectiveness in:
- Partial seizures with or without secondary generalization
- Paroxysmal kinesigenic dyskinesia (PKD), where it works as a voltage-gated sodium channel blocker 5
Important Clinical Considerations
No neurotransmitter receptor interactions: No significant interactions with brain neurotransmitter or modulator receptor sites have been demonstrated 1
Anticonvulsant activity: Oxcarbazepine and MHD protect against electrically induced tonic extension seizures and, to a lesser degree, chemically induced clonic seizures 1
No tolerance development: No attenuation of anticonvulsive activity was observed in animal models with daily treatment 1
The understanding of oxcarbazepine's mechanism of action helps explain its efficacy profile and guides appropriate clinical use in seizure disorders and other conditions where neuronal hyperexcitability plays a role.