All cells in the human body have a resting membrane potential, formed by the difference in net charge between the two sides of the plasma membrane. In neurons, this becomes particularly important since neuron function relies on rapid changes in the membrane potential. Figure 1 shows the normal action potential in relation to the membrane potential.
Several drugs act directly on ion channels in the brain to exert their effect. Drugs used in the treatment of epilepsy, where rapid excitation of neurons results in seizure, act by affecting voltage-dependent sodium channels. Other drugs, such as tiagabine, increase the effect of inhibitory receptors, thereby reducing the probability of firing an action potential. Anti-convulsive compounds such as carbamazopine are also used in the treatment of epilepsy, however, do not act on the central nervous system. Instead, they block neuron signaling in peripheral tissues.
Continued therapy with certain compounds, however, leads to a phenomenon known as tolerance, in which the drug no longer gives the desired effect. Progressively higher doses of the same drug are required to elicit therapeutic effect, until the concentrations used are no longer physiologically acceptable.