Biomaterial Database

Comparative actions of phenytoin and other anticonvulsant drugs on potassium- and veratridine-stimulated calcium uptake in synaptosomes. 1982

J A Ferrendelli, and S Daniels-McQueen

The actions of phenytoin and several anticonvulsants drugs on veratridine-stimulated (Na-dependent) and K-stimulated (Na-independent) Ca uptake were studied in isolated nerve terminals (synaptosomes) from rat cerebral cortex. Phenytoin inhibits both veratridine- and K-induced Ca uptake but is more potent against veratridine. Inhibition of veratridine-stimulated Ca uptake by phenytoin appears to be a competitive relationship, whereas the interaction between K and phenytoin is noncompetitive. Hydroxyphenyl-phenylhydantoin, mephenytoin and ethylphenylhydantoin have actions similar to phenytoin but all are substantially less potent. Carbamazepine, phenobarbital, diazepam and lidocaine also inhibit veratridine- and K-stimulated Ca uptake, but ethosuximide and valproic acid are ineffective. Only carbamazepine and lidocaine have a relatively selective action against veratridine which is similar to phenytoin, and only these three drugs are active at concentrations which approximate their clinically effective anticonvulsant blood levels. The results of this study, in conjunction with reported data, suggest that phenytoin inhibits Na and Ca conductances in nervous tissue by separate and probably independent mechanisms. The present data also lead to the hypothesis that inhibition of Na uptake (perhaps associated with inhibition of Ca uptake) in nervous tissues is a mechanism of action responsible for some of the selective antiepileptic effects and/or analgesic effects of phenytoin, carbamazepine and lidocaine.

UI	MeSH Term	Description	Entries
D008345	Manganese	A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D010672	Phenytoin	An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.	Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006827	Hydantoins	Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS.	Hydantoin,Imidazolidine-2,4-Diones,Imidazolidine 2,4 Diones
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000927	Anticonvulsants	Drugs used to prevent SEIZURES or reduce their severity.	Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D013574	Synaptosomes	Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.	Synaptosome
D013779	Tetrodotoxin	An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.	Fugu Toxin,Tarichatoxin,Tetradotoxin,Toxin, Fugu