Tricyclic anticonvulsants: mechanisms of action

Abstract

Two aspects of neuronal function are particularly relevant to the known actions of antiepileptic drugs (AEDs): voltage-dependent ionic membrane conductances (especially sodium, potassium, and calcium); and synaptic actions of neurotransmitters, particularly c-aminobutyric acid (GABA), glutamate, and acetylcholine. Inhibitory actions in the central nervous system (CNS) are mediated principally by GABA. Other neurotransmitters, including norepinephrine, dopamine, and serotonin, also have inhibitory properties [1]. GABA receptors, which have been cloned, are composed of a GABAA receptor, a barbiturate receptor, and a benzodiazepine receptor, which all surround the chloride channel [2]. Neurons that secrete the excitatory amino acid L-glutamate are ubiquitous throughout the CNS. Cholinergic neurons extend from the septum and basal forebrain to the cortex, including the hippocampus. Recent evidence suggests a role for acetylcholine in epileptogenesis; e.g., excised temporal lobectomy tissues show increased concentrations of acetylcholinesterase compared with what is expected [1].