Carbamazepine (NSC-169864) is a tricyclic compound chemically related to tricyclic antidepressants (TCA) with anticonvulsant and analgesic properties. Carbamazepine exerts its anticonvulsant activity by reducing polysynaptic responses and blocking post-tetanic potentiation. Its analgesic activity is not understood; however, carbamazepine is commonly used to treat pain associated with trigeminal neuralgia.

Treatment with Carbamazepine (25 mg/kg) significantly increases the levels of hippocampal dopamine, dihydroxyphenylalanine (DOPA), striatal homovanillic acid, and 3,4-dihydroxyphenylacetic acid, with these effects being dose-dependent. However, a higher dose of Carbamazepine (50 mg/kg) markedly reduces the overall hippocampal homovanillic acid and striatal DOPA and dopamine levels, while not affecting hippocampal dopamine, DOPA, and DOPAC levels, nor overall striatal DOPAC and homovanillic acid. At a dose of Carbamazepine (100 mg/kg, i.p.), there is a dose-dependent significant increase in the concentrations of neuroactive steroids in rat plasma corticosterone.

In the presence of batrachotoxin, carbamazepine did not alter the binding of scorpion toxin (125I-labeled) to synaptosomes; however, upon the addition of 1.25 μM batrachotoxin, carbamazepine concentration dependently inhibited the enhancement of batrachotoxin-dependent scorpion toxin binding (IC50: 260 μM) via regulatory sites of the toxin alkaloid. Importantly, carbamazepine had no effect on [3H]saxitoxin binding. When acting on rat brain synaptosomes, carbamazepine impeded the binding of [3H]Batrachotoxinin A 20-α-benzoate to the voltage-sensitive sodium channel site (IC50: 131 μM), thereby reducing the ion flow activity of the sodium channels. As the dissociation rate of the ligand from the receptor-ligand complex increased, carbamazepine, despite decreasing receptor affinity, did not change the maximal binding capacity in Scatchard analyses of [3H]Batrachotoxinin A 20-α-benzoate to synaptosomes, suggesting that binding of [3H]Batrachotoxinin A 20-α-benzoate inhibits conformational changes associated with anticonvulsant effects.