the treatment of trigeminal neuralgia but has proved useful for epilepsy as well. Chemistry Although not obvious from a two-dimensional representation of its structure, carbamazepine has many similarities to phenytoin.The ureide moiety (-N-CO-NH2) present in the heterocyclic ring of most antiseizure drugs is also present in carbamazepine.Three-dimensional structural studies indicate that its spatial conformation is similar to that of phenytoin. Mechanism of Action The mechanism of action of carbamazepine appears to be similar to that of phenytoin Like phenytoin,carbamazepine shows activity against maximal electroshock seizures. Carbamazepine,like phenytoin,blocks sodium channels at therapeutic concentrations and inhibits high-frequency repetitive firing in neurons in culture (Figure 24-2).It also acts presynaptically to decrease synaptic transmission.These effects probably account for the anticonvulsant action of carbamazepine.Binding studies show that carbamazepine interacts with adenosine receptors,but the functional significance of this observation is not known. Clinical Use Although carbamazepine has long been considered a drug of choice for both partial seizures and generalized tonic-clonic seizures,some of the newer antiseizure drugs are beginning to displace it from this role.Carbamazepine is not sedative in its usual therapeutic range.The drug is also very effective in some patients with trigeminal neuralgia,although older patients may tolerate higher doses poorly,with ataxia and unsteadiness.Carbamazepine is also useful in some patients with mania (bipolar disorder). Pharmacokinetics The rate of absorption of carbamazepine varies widely among patients,although almost complete absorption apparently occurs in all.Peak levels are usually achieved 6-8 hours after administration.Slowing absorption by giving the drug after meals helps the patient tolerate larger total daily doses. Distribution is slow,and the volume of distribution is roughly 1 L/kg.The drug is only 70%bound to plasma proteins;no displacement of other drugs from protein binding sites has been observed. Carbamazepine has a very low systemic clearance of approximately 1 L/kg/d at the start of therapy.The drug has a notable ability to induce microsomal enzymes.the treatment of trigeminal neuralgia but has proved useful for epilepsy as well. Chemistry Although not obvious from a two-dimensional representation of its structure, carbamazepine has many similarities to phenytoin. The ureide moiety (-N-CO-NH2) present in the heterocyclic ring of most antiseizure drugs is also present in carbamazepine. Three-dimensional structural studies indicate that its spatial conformation is similar to that of phenytoin. Mechanism of Action The mechanism of action of carbamazepine appears to be similar to that of phenytoin. Like phenytoin, carbamazepine shows activity against maximal electroshock seizures. Carbamazepine, like phenytoin, blocks sodium channels at therapeutic concentrations and inhibits high-frequency repetitive firing in neurons in culture (Figure 24-2). It also acts presynaptically to decrease synaptic transmission. These effects probably account for the anticonvulsant action of carbamazepine. Binding studies show that carbamazepine interacts with adenosine receptors, but the functional significance of this observation is not known. Clinical Use Although carbamazepine has long been considered a drug of choice for both partial seizures and generalized tonic-clonic seizures, some of the newer antiseizure drugs are beginning to displace it from this role. Carbamazepine is not sedative in its usual therapeutic range. The drug is also very effective in some patients with trigeminal neuralgia, although older patients may tolerate higher doses poorly, with ataxia and unsteadiness. Carbamazepine is also useful in some patients with mania (bipolar disorder). Pharmacokinetics The rate of absorption of carbamazepine varies widely among patients, although almost complete absorption apparently occurs in all. Peak levels are usually achieved 6-8 hours after administration. Slowing absorption by giving the drug after meals helps the patient tolerate larger total daily doses. Distribution is slow, and the volume of distribution is roughly 1 L/kg. The drug is only 70% bound to plasma proteins; no displacement of other drugs from protein binding sites has been observed. Carbamazepine has a very low systemic clearance of approximately 1 L/kg/d at the start of therapy. The drug has a notable ability to induce microsomal enzymes