Anticonvulsant drugs: mechanisms of action.

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Macdonald RL, McLean MJ

Anticonvulsant drugs: mechanisms of action.

Adv Neurol. 1986;44:713-36.

PubMed ID

2871724 [ View in PubMed

]

Abstract

A variety of the anticonvulsant drugs, including carbamazepine, phenytoin, primidone, phenobarbital, clonazepam, valproic acid, and ethosuximide, are available for use in the treatment of patients with seizure disorders. These anticonvulsants vary in their efficacy against experimental seizures in animals and against seizures in humans. The mechanistic basis for this variability in anticonvulsant drug action remains uncertain, but numerous mechanisms of action have been proposed. We have used mouse neurons in primary dissociated cell culture to study the action of these anticonvulsant drugs on several aspects of membrane excitability and synaptic transmission. We have proposed that the anticonvulsant drugs can be classified according to their actions on sustained high frequency repetitive firing (SRF) of action potentials and on postsynaptic gamma-aminobutyric acid (GABA) responses. Phenytoin and carbamazepine were both effective against SRF but did not modify postsynaptic GABA responses at therapeutically relevant concentrations. Phenobarbital, benzodiazepines, and valproic acid modified both SRF and postsynaptic GABA responses. Ethosuximide had no effect on SRF or GABAergic mechanisms. Based on these results, we have proposed that blockade of SRF may underlie the action of phenytoin, carbamazepine, phenobarbital, valproic acid, and benzodiazepines against generalized tonic-clonic seizures in humans and maximal electroshock seizures in animals. Enhancement of GABAergic synaptic transmission may underlie efficacy of benzodiazepines and valproic-acid drugs against generalized absence seizures in humans and pentylenetetrazol-induced seizures in experimental animals. The mechanism of action of ethosuximide against generalized absence seizures in humans and pentylenetetrazol-induced seizures in experimental animals may be by a third, as yet unknown, mechanism.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Phenobarbital	Gamma-aminobutyric acid receptor subunit alpha-1	Protein	Humans	Yes	Potentiator	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
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Amobarbital Primidone	The risk or severity of adverse effects can be increased when Primidone is combined with Amobarbital.
Amobarbital Methylphenobarbital	The risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Amobarbital.
Amobarbital Phenobarbital	The risk or severity of adverse effects can be increased when Phenobarbital is combined with Amobarbital.
Butabarbital Primidone	The risk or severity of adverse effects can be increased when Primidone is combined with Butabarbital.
Butabarbital Methylphenobarbital	The risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Butabarbital.