Abstract
Although the mechanisms of anticonvulsant action remain uncertain, numerous physiological and biochemical correlates of such action have been documented, and it is possible that one or more of such correlates bears a causal (i.e., mechanistic) relationship with action. The physiological correlates of anticonvulsant action are discussed in Chap. 23; the present chapter will focus on biochemical correlates, with an analysis of the possible mechanistic significance of each.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Agarwal SL, Bhargava V (1964) Effect of drugs on brain acetylcholine level in rats. Indian J Med Res 52: 1179–1182
Anlezark G, Horton RW, Meldrum BS, Sawaya MCB (1976) Anticonvulsant action of eth- anolamine-O-sulfate and di-zi-propylacetate and the metabolism of y-aminobutyric acid ( GABA) in mice with audiogenic seizures. Biochem Pharmacol 25: 413–417
Ayala GF, Lin G, Johnston D (1977) The mechanism of action of diphenylhydantoin on invertebrate neurons: I. Effects on basic membrane properties. Brain Res 121: 245–258
Baker PF, Blaustein MP, Manil J, Steinhardt RA (1969) The influence of calcium on sodium efflux in squid axons. J Physiol (Lond) 200: 431–458
Baker PF, Hodgkin AC, Ridgway EF (1971) Depolarization and calcium entry in squid giant axons. J Physiol (Lond) 218: 709–755
Baskin SI, Dutta S, Marks BH (1973) The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea pig heart. Br J Pharmacol 47: 85–96
Bianchi C, Beani L, Bertelli A (1975) Effects of some anti-epileptic drugs on brain acetylcholine. Neuropharmacology 14: 327–332
Bowling AC, DeLorenzo RJ (1982) Micromolar affinity benzodiazepine receptors: identification and characterization in central nervous system. Science 216: 1247–1250
Bronsted HE, Woodbury DM (1973) Uptake and distribution of 3H-ouabain in brain and other tissues of developing rats. In: Boreus L (ed) Fetal pharmacology. Raven, New York, pp 89–92
Camerman A, Camerman N (1970) Diphenylhydantoin and diazepam: molecular structure similarities and steric basis of anticonvulsant activity. Science 168: 1457–1458
Chwen AY, Leslie SW (1981) Enhancement of 45Ca+ + binding to acidic lipids by barbiturates, diphenylhydantoin, and ethanol. J Neurochem 36: 1865–1867
Cohen MS, Bower RH, Fidler SM, Hohnsonbaugh RE, Sode J (1973) Inhibition of insulin release by diphenylhydantoin and diazoxide in a patient with benign insulinoma. Lancet 1: 40–41
Delgado-Escueta AV, Horan MP (1980) Antiepileptic drugs. Phenytoin: biochemical membrane studies. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanisms of action. Raven, New York, pp 337–396
DeLorenzo RJ (1977) Antagonistic action of diphenylhydantoin and calcium on the level of phosphorylation of particular rat and human brain proteins. Brain Res 134: 125–138
DeLorenzo RJ (1980) Antiepileptic drugs. Phenytoin: calcium- and calmodulin-dependent protein phosphorylation and neurotransmitter release. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanism of action. Raven, New York, pp 399–414
DeSousa RC, Grosso A (1973) Effects of diphenylhydantoin on transport processes in frog skin (Rana ridibunda). Experientia 29: 1097–1098
Deupree JD (1977) The role or non-role of ATPase activation by phenytoin in the stabilization of excitable membranes. Epilepsia 18: 309–315
DeWeer P (1980) Antiepileptic drugs. Phenytoin: blockage of resting sodium channels. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanisms of action. Raven, New York, pp 353–361
Downes H, Williams JK (1969) Effects of a convulsant barbiturate on the spinal monosynaptic pathway. J Pharmacol Exp Ther 168: 283–289
Dray A, Bowery NH (1979) GABA convulsants and their interactions with central depressant agents. In: Krogsgaard-Larsen P, Scheel-Kriiger J, Kofod H (eds) GABA- neurotransmitters. Munksgaard, Copenhagen, pp 376–389
Enna SJ, Maggi A, Worms P, Lloyd KG (1980) Muscimol: brain penetration and anticonvulsant potency following GABA-T inhibition. Brain Res Bull 5 (Suppl 2): 461–464
Escueta AV, Davidson O, Hartwig G, Reilly E (1974) The freezing lesion. III. The effects of diphenylhydantoin on potassium transport within the nerve terminals from the primary foci. Brain Res 86: 85–96
Ferrendelli J A, Daniels-McQueen S (1982) Comparative actions of phenytoin and other anticonvulsant drugs on potassium- and veratridine-stimulated calcium uptake in synaptosomes. J Pharmacol Exp Ther 220-29–343
Ferrendelli J A, Kinscherf DA (1977) Phenytoin: effects on calcium flux and cyclic nucleotides. Epilepsia 18: 331–336
Fertziger AP, Liuzzi SE, Dunham PB (1971) Diphenylhydantoin (Dilantin): stimulator of potassium influx in lobster axons. Brain Res 33: 592–596
Festoff BW, Appel SH (1968) Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase. J Clin Invest 47: 2752–2758
Fichman MP, Kleeman CR, Bethune JE (1970) Inhibition of antidiuretic hormone secretion by diphenylhydantoin. Arch Neurol 22: 45–53
Fowler LJ, Beckford J, John RA (1975) An analysis of the kinetics of the inhibition of rabbit brain y-aminobutyrate aminotransferase by sodium w-dipropylacetate and some other simple carboxylic acids. Biochem Pharmacol 24: 1267–1270
Frey HH, Loscher W (1980) Cetyl GABA: effect on convulsant thresholds in mice and acute toxicity. Neuropharmocology 19: 217–220
Gerich JE, Charles MA, Levin SR, Forsham PH, Grodsky GM (1972) In vitro inhibition of pancreatic glucagon secretion by diphenylhydantoin. J Clin Endocrin Metab 35: 823–824
Gilbert JC, Wyllie MG (1976) Effects of anticonvulsant and convulsant drugs on the ATPase activities of synaptosomes and their components. Br J Pharmacol 56: 49–57
Godin Y, Heiner L, Mark J, Mandel P (1969) Effects of di-H-propylacetate, an anticonvulsive compound, on GABA metabolism. J Neurochem 16: 869–873
Goldberg MA (1980) Antiepileptic drugs. Phenytoin: binding. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanisms of action. Raven, New York, pp 323–337
Goldstein RE, Penzotti C, Kuehl KS, Prindle HK Jr, Hall CA, Titus EO (1973) Correlation of antiarrhythmic effects of diphenylhydantoin with digoxin-induced changes in myocardial contractility, sodium-potassium adenosine triphosphatase activity, and potas-sium efflux. Circ Res 33: 823–824
Greenlee DV, Van Ness PC, Olsen RW (1978) Gamma-aminobutyric acid binding in mammalian brain: receptor-like specificity of sodium independent sites. J Neurochem 31: 933–938
Gross GJ, Woodbury DM (1972) Effects of pentylenetetrazole on ion transport in the isolated toad bladder. J Pharmacol Exp Ther 181: 257–272
Guidotti A, Toffano G, Baraldi M, Schwartz JP, Costa E (1979) Molecular mechanism for the facilitation of GABA receptor function by benzodiazepines. In: Krogsgaard-Larsen P, Scheel-Kriiger J, Kofod H (eds) GABA-neurotransmitters. Munksgaard, Copenhagen, pp 406–415
Gutman Y, Boonyaviroj P (1977) Mechanism of inhibition of catecholamine release from adrenal medulla by diphenylhydantoin and by low concentrations of ouabain (10−10 M). Naunyn Schmiedebergs Arch Pharmacol 296: 293–296
Hammond EJ, Wilder BJ, Villarreal HJ, Perchalski RJ (1981) Central nervous system penetration of valproic acid. Epilepsia 22: 227
Harvey PKP, Bradford HF, Davison AN (1975) The inhibitory effect of sodium w-dipropyl acetate on the degradative enzymes of the GABA shunt. FEBS Lett 52: 251–254
Hasbani M, Pincus J, Lee SH (1974) Diphenylhydantoin and calcium movement in lobster nerves. Arch Neurol 31: 250–254
Heinemann LI, Lux HD (1973) Effects of diphenylhydantoin on extracellular [K+] in cat cortex. Electroencephalogr Clin Neurophysiol 34: 735
Johnston GAR (1978) Neuropharmacology of amino acid inhibitory transmitters. Ann Rev Pharmacol Toxicol 18: 269–289
Katz B, Miledi R (1970) Further study of the role of calcium in synaptic transmission. J Physiol (Lond) 207: 789–801
Kootstra A, Woodhouse SP (1974) The effect of diphenylhydantoin on the Na+-K+-stimulated ouabain inhibited ATPase. Proc Univ Otago Med Sch 52: 6–7
Krogsgaard-Larsen P, Hjeds H, Curtis DR, Lodge D, Johnston GAR (1979) Dihy- dromuscimol, thiomuscimol and related heterocyclic compounds as GABA analogues. J Neurochem 32: 1717–1724
Leeb-Lundberg F, Snowman A, Olsen RW (1981) Some anticonvulsants interact with the GABA receptor-ionophore complex at barbiturate/picrotoxin receptor sites. Fed Proc 40: 309
Lewin E, Bleck V (1977) The effect of diphenylhydantoin administration on sodium-potassium-activated ATPase in cortex. Neurology 21: 647–651
Leznicki AL, Dymecki J (1974) The effect of certain anticonvulsants in vitro and in vivo on enzyme activities in rat brain. Neurol Neurochir Pol 24: 413–419
Lipicky RJ, Gilbert DK, Stillman IM (1972) Diphenylhydantoin inhibition of sodium conductance in squid giant axon. Proc Natl Acad Sci NY 69: 1758–1760
Maitre M, Ossola L, Mandel P (1976) In vitro studies into the effect of inhibition of rat brain succinic semialdehyde dehydrogenase on GABA synthesis and degradation. FEBS Lett 72: 53–57
McDonald RL, Barker JL (1978) Specific antagonism of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of convulsant action. Neurology (Minneap) 28: 325–330
McDonald RL, Barker JL (1979) Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action. Brain Res 167: 323–336
McLennan H, Elliot KAC (1951) Effects of convulsant and narcotic drugs on acetylcholine synthesis. J Pharmacol Exp Ther 103: 35–43
Meldrum B, Hortin R (1980) Effects of the bicyclic GABA agonist, THIP, on myoclonic and seizure responses in mice and baboons with reflex epilepsy. Eur J Pharmacol 61: 231–237
Meldrum B, Pedley T, Horton R, Anlezark G, Franks A (1980) Epileptogenic and anticonvulsant effects of GABA agonists and GABA uptake inhibitors. Brain Res Bull 5 (Suppl 2): 685–690
Miledi R (1973) Transmitter release induced by injection of calcium ions into nerve terminals. Proc R Soc Lond (Biol) 183: 421–425
Mittler JC, Glick SM (1972) Radioimmunoassayable oxytocin release from isolated neural lobes; responses to ions and drugs. IV International congress of endocrinology, Washington, 1972. Excerpta Medica Abstracts of Communications No. 177, p 46
Nachshen DA, Blaustein MP (1980) Some properties of potassium-stimulated calcium influx in presynaptic nerve endings. J Gen Physiol 76: 709–728
Nau H, Loscher W (1982) Valproic acid: brain and plasma levels of the drug and its metabolites, anticonvulsant effects and y-aminobutyric acid ( GABA) metabolism in the mouse. J Pharmacol Exp Ther 220: 654–659
Nicoll RA, Wojtowicz JM (1980) The effects of pentobarbital and related compounds on frog motoneurons. Brain Res 191: 225–237
Nosek TM (1981) How valproate and phenytoin affect the ionic conductance and active transport characteristics of the crayfish giant axon. Epilepsia 22: 651–665
Olsen RW (1981) The GABA postsynaptic membrane receptor-ionophore complex. Site of action of convulsant and anticonvulsant drugs. Mol Cell Biochem 39: 261–279
Olsen RW, Lamar EE, Bayless JD (1977) Calcium-induced release of y-aminobutyric acid from synaptosomes: effects of tranquilliser drugs. J Neurochem 28: 299–305
Olsen RW, Greenlee D, Van Ness P, Ticku MK (1978) In: Fonnum F (ed) Amino acids as chemical transmitters. Plenum, New York, pp 467–486
Olsen RW, Ticku MK, Greenlee D, Van Ness P (1979) GABA receptor and ionophore binding sites - interaction with various drugs. In: Krogsgaard-Larsen P, Scheel-Kriiger J, Kofod H (eds) GABA-neurotransmitters. Munksgaard, Copenhagen, pp 165–178
Olsen RW, Leeb-Lundberg F, Napias C (1980) Picrotoxin and convulsant binding sites in mammalian brain. Brain Res Bull 5 (Suppl 2): 217–2213
Ostravskaya RU, Molodavkin GM, Porfireva RP, Zubovskaya AM (1975) Mechanism of the anticonvulsant action of diazepam. Bull Exp Biol Med 79: 270–273
Patsalos PN, Lascelles PT (1981) Changes in regional brain levels of amino acid putative neurotransmitters after prolonged treatment with the anticonvulsant drugs diphenyl-hydantoin, phenobarbitone, sodium valproate, ethosuximide, and sulthiame in the rat. J Neurochem 36: 688–695
Pincus JH (1972) Diphenylhydantoin and ion flux in lobster nerve. Arch Neurol 26: 4–10
Pincus JH, Grove I, Marino BB, Glaser GB (1970) Studies on the mechanism of action of diphenylhydantoin. Arch Neurol 22: 566–571
Roses AD, Butterfield A, Appel SH, Chestnut DR (1975) Phenytoin and membrane fluidity in myotonic dystrophy. Arch Neurol 33: 535–538
Saad SF, El-Masry AM, Scott PM (1972) Influence of certain anticonvulsants on the concentration of gamma-aminobutyric acid in the cerebral hemisphere of mice. Eur J. Pharmacol 17: 386–392
Sawaya MCB, Horton RW, Meldrum BS (1975) Effects of anticonvulsant drugs on the cerebral enzymes metabolizing GABA. Epilepsia 16: 649–655
Schant CL, Davis FA, Marder V (1974) Effects of carbamazepine on the ionic conductance of Myxicola giant axons. J Pharmacol Exp Ther 189–538–543
Schlosser W, Franco S (1979) Reduction of y-aminobutyric acid ( GABA)-mediated transmission by a convulsant benzodiazepine. J Pharmacol Exp Ther 211: 290–295
Schwartz A, Lindenmayer GE, Allen JC (1975) The sodium-potassium adenosine triphosphatase: pharmacological and biochemical aspects. Pharmacol Rev 27: 3–134
Siegle GJ, Goodwin BB (1972) Sodium-potassium-activated adenosine triphosphatase of brain microsomes: modification of sodium inhibition by diphenylhydantoin. J Clin Invest 51: 1164–1169
Slater GE, Johnston D (1978) Sodium valproate increases potassium conductance in Aplysio. neurons. Epilepsia 19: 379–384
Sohn RS, Ferrendelli J A (1973) Inhibition of Ca+ + transport into rat brain synaptosomes by diphenylhydantoin ( DPH ). J Pharmacol Exp Ther 185: 272–275
Sohn RS, Ferrendelli J A (1976) Anticonvulsant drug mechanisms. Phenytoin, phenobarbital, and ethosuximide and calcium flux in isolated presynaptic endings. Arch Neurol 33: 626–629
Spain RC, Chidsey CA (1971) Myocardial Na/K adenosine triphosphatase activity during reversal of ouabain toxicity with diphenylhydantoin. J Pharmacol Exp Ther 179: 594–598
Ticku MK, Olsen RW (1978) Interaction of barbiturates with dihydropicrotoxinin binding sites related to the GABA receptor-ionophore system. Life Sci 22: 1643–1651
Ticku MK, Ban M, Olsen RW (1978) Binding of [3H]-dihydropicrotoxinin, a y-aminobutyric acid synaptic antagonist, to rat brain membranes. Mol Pharmacol 14: 391–402
Vernadakis A, Woodbury DM (1960) Effects of diphenylhydantoin and adrenocortical steroids on free glutamic acid, glutamine and gamma-aminobutyric acid concentrations of rat cerebral cortex. In: Roberts E (ed) Inhibition in the nervous system and gamma-aminobutyric acid, Pergamon, Oxford, pp 242–248
Watson EL, Woodbury DM (1972) Effects of diphenylhydantoin on active sodium transport in frog skin. J Pharmacol Exp Ther 180: 767–776
Watson EL, Woodbury DM (1973) The effect of diphenylhydantoin and ouabain, alone and in combination, on the electrocardiogram and on cellular electrolytes of guinea pig heart and skeletal muscle. Arch Int Pharmacodyn 20: 389–399
Weinberger J, Nichlas WJ, Berl S (1976) Mechanism of action of anticonvulsants. Neurology (Minneap) 26: 162–166
Whittle SR, Turner A J (1978) Effects of the anticonvulsant sodium valproate on y-amino- butyrate and aldehyde metabolism in ox brain. J Neurochem 31: 1453–1459
Wilensky AJ, Lowden J A (1972) The inhibitor effect of diphenylhydantoin on microsomal ATPase. Life Sci 11: 319–327
Woodbury DM (1955) Effects of diphenylhydantoin on electrolytes and radiosodium turnover in brain and other tissues of normal, hyponatremic and postictal rats. J Pharmacol Exp Ther 115: 74–95
Woodbury DM (1969) Role of pharmacological factors in the evaluation of anticonvulsant drugs. Epilepsia 10: 121–143
Woodbury DM (1974) Antiepileptic drugs: pharmacology and mechanisms of action. In: Harris P, Mawdsley C (eds) Epilepsy. Proceedings of the Hans Berger centenary symposium, Churchill Livingstone, Edinburgh, pp 78–95
Woodbury DM (1978) Metabolites and the mechanisms of action of antiepileptic drugs. In: Meinardi H, Rowan AJ (eds) Advances in epileptology, 1977: Psychology, pharmacotherapy, and new diagnostic approaches. Proceedings of the thirteenth congress of the International League Against Epilepsy and ninth symposium of the International Bureau for Epilepsy, Amsterdam, September 1977, Swets and Zeitlinger, Amsterdam, pp 134–150
Woodbury DM (1980) Antiepileptic drugs. Phenytoin: proposed mechanisms of anticonvulsant action. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanisms of action. Raven, New York, pp 447–471
Yaari Y, Pincus JH, Argov Z (1977) Depression of synaptic transmission by diphenylhydantoin. Ann Neurol 1: 334–338
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Jones, G.L., Woodbury, D.M. (1985). Biochemistry. In: Frey, HH., Janz, D. (eds) Antiepileptic Drugs. Handbook of Experimental Pharmacology, vol 74. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69518-6_10
Download citation
DOI: https://doi.org/10.1007/978-3-642-69518-6_10
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-69520-9
Online ISBN: 978-3-642-69518-6
eBook Packages: Springer Book Archive