A pharmacological analysis of the mechanism of action of ethosuximide

: Ethosuximide is one of the means of treatment of minor epilepsy but hardly any data on its mechanism of action are available in the literature. Anticonvulsant agents are known to bring about changes in the functions and in the interaction between some of the mediator systems within the central nervous system. An assessment of the status of neuromediator systems can be made on the basis of the response of isolated smooth muscle strips to the action of agonists and antagonists of various receptors. It was found by the pharmacological analysis of isolated strips from the rat stomach (antrum and corpus strips), the seminal duct and the cervical vein that ethosuximide induces a reduction in the physical contractile activity and the tone of smooth muscle preparations. Smooth muscle relaxation caused by ethosuximide is not blocked by different receptor inhibitors such as dihydroergotamine, propranolol, atropine, chlorpromazine, haloperidod and indomethacin. Ethosuximide causes a significant reduction in the physical contraction of smooth muscles produced by potassium chloride depolarization, with a stronger impact on the subsequent tonic contraction caused by calcium ions. A reduction in the potassium content of the solution has no effect on the nature of the action of ethosutimide. It is thus assumed that the probable mechanism of action of ethosuximide consists in lowering calcium transport since the inhibitors of calcium transport sodium nitroprusside and verapamil intensify the blocking effect of ethosuximide on smooth muscle contractile activity.