From the Guidelines
Carbamazepine primarily works by blocking voltage-dependent sodium channels in neuronal cell membranes, which inhibits the generation and propagation of action potentials. This mechanism stabilizes hyperexcited neural membranes, reduces repetitive neuronal firing, and prevents the spread of seizure activity. The drug selectively acts on neurons that are firing rapidly and repetitively, as occurs during seizures, while having minimal effect on normal neuronal activity.
Key Mechanisms of Action
- Blocking voltage-dependent sodium channels
- Reducing the release of glutamate (an excitatory neurotransmitter)
- Affecting GABA receptors (the main inhibitory neurotransmitter system)
- Modulating calcium channels and adenosine receptors These combined actions make carbamazepine effective for treating seizure disorders, trigeminal neuralgia, and bipolar disorder, as supported by recent studies 1.
Clinical Considerations
- The initial dosage of carbamazepine for PKD treatment is recommended to be 50 mg and can be adjusted according to the practical effect 1
- HLA-B*15:02 screening should be implemented before initiating treatment to reduce the risk of adverse cutaneous reactions 1
- The medication should be taken at bedtime to minimize the adverse effect of dizziness caused by carbamazepine 1 The drug's therapeutic effects typically require steady blood levels, which is why it's usually administered in divided doses and often started at lower doses with gradual increases to minimize side effects.
Treatment Guidelines
- More than 85% of patients can achieve complete remission with low-dose carbamazepine (50–200 mg/day) or oxcarbazepine (75–300 mg/day) 1
- Individualized treatment is recommended, and adequate communication regarding the prognosis of the disease, the adverse effects of the medication and the expected outcome of the treatment is warranted before the use of medication 1
From the FDA Drug Label
Mechanism of Action Carbamazepine has demonstrated anticonvulsant properties in rats and mice with electrically and chemically induced seizures It appears to act by reducing polysynaptic responses and blocking the post-tetanic potentiation. The mechanism of action remains unknown.
The mechanism of action of carbamazepine is not fully understood, but it appears to act by:
- Reducing polysynaptic responses
- Blocking the post-tetanic potentiation 2
From the Research
Mechanism of Action of Carbamazepine
The mechanism of action of carbamazepine is not completely elucidated and is still a matter of debate 3. However, the available data indicate that the anticonvulsant efficacy of carbamazepine is mainly due to the inhibition of sodium channel activity 3, 4, 5.
Inhibition of Sodium Channel Activity
- Carbamazepine blocks sodium channels by binding preferentially to the inactivated state, thereby allowing normal neuronal firing while blocking ictal activity 4.
- The inhibition of sodium channel activity reduces action potential amplitude, but may paradoxically increase action potential firing rates in certain conditions 4.
- The effect of carbamazepine on sodium channels depends on the resting membrane potential and the specific makeup of conductances in the network 4.
Other Mechanisms
- Carbamazepine may also act on other mechanisms, such as:
- "Peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems 6.
- GABAB (baclofen-like) actions, which appear to be involved in antinociceptive, but not anticonvulsant, effects 6.
- Increasing acetylcholine in the striatum, decreasing probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decreasing CSF norepinephrine in manic patients, inhibiting adenylate cyclase activity, decreasing GABA turnover, or acting as a vasopressin agonist 6.