Field-potential assay of antiepileptic drugs in the hippocampal slice. 1988

D Ashton, and R Willems, and E de Prins, and A Wauquier
Department of Neuropharmacology, Janssen Pharmaceutica, Beerse, Belgium.

The effects of nine clinically active antiepileptic drugs and the NMDA antagonist 2-amino-7-phosphonoheptanoic acid (2-APH) were examined in three models in the in vitro hippocampal slice. In the "low Mg2+" model, removal of Mg2+ from the perfusion fluid increased excitatory neurotransmission and led to epileptogenic field potentials. In the "low Ca2+" model, decrease of Ca2+ and increase of Mg2+ and K+ in the perfusion fluid induced spontaneous "bursts" in the absence of synaptic transmission. Paired-pulse stimulation was used to estimate the strength of recurrent inhibition in the "inhibition" model. The rank order of the potency of the compounds to antagonize the second epileptogenic population spike in the low Mg2+ model was 2-APH greater than pentobarbital greater than midazolam greater than phenytoin greater than carbamazepine greater than chlordiazepoxide greater than phenobarbital = flurazepam. Ethosuximide and valproate were inactive. In the low Ca2+ model, the rank order of the potency of the drugs to antagonize spontaneous epileptogenic bursts was phenytoin greater than carbamazepine greater than midazolam greater than pentobarbital greater than chlordiazepoxide greater than flurazepam greater than phenobarbital. 2-APH, ethosuximide, and valproate were inactive. Only pentobarbital was active in the inhibition model. These experiments demonstrate the potential of in vitro tests in the hippocampus to reveal profiles of anticonvulsant activity.

UI MeSH Term Description Entries
D008274 Magnesium A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D009433 Neural Inhibition The function of opposing or restraining the excitation of neurons or their target excitable cells. Inhibition, Neural
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
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
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
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

Related Publications

D Ashton, and R Willems, and E de Prins, and A Wauquier
August 2001, Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology,
D Ashton, and R Willems, and E de Prins, and A Wauquier
November 2012, Epilepsia,
D Ashton, and R Willems, and E de Prins, and A Wauquier
June 2008, British journal of pharmacology,
D Ashton, and R Willems, and E de Prins, and A Wauquier
January 1994, Neuroscience letters,
D Ashton, and R Willems, and E de Prins, and A Wauquier
August 2001, Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology,
D Ashton, and R Willems, and E de Prins, and A Wauquier
October 1994, Sheng li ke xue jin zhan [Progress in physiology],
D Ashton, and R Willems, and E de Prins, and A Wauquier
February 1982, Japanese journal of pharmacology,
D Ashton, and R Willems, and E de Prins, and A Wauquier
June 1988, Brain research,
D Ashton, and R Willems, and E de Prins, and A Wauquier
June 1993, Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao,
D Ashton, and R Willems, and E de Prins, and A Wauquier
April 1949, Journal of the American Pharmaceutical Association. American Pharmaceutical Association,
Copied contents to your clipboard!