Reduction of the frequency of occurrence of low magnesium induced field potentials in the hippocampus slice preparation of guinea pigs: a good screening tool for calcium antagonistic effects of anticonvulsant and antipsychotic drugs.
An ideal model for in vitro research purposes of epilepsies should reflect the different clinical aspects of epileptic seizures, both in vivo and, as far as comparisons are possible, in vitro. It should induce long-term changes on a cellular level analogous to what is observed in epileptic patients, and should be triggered by varying endogenous physiological processes without additional exogenous drugs. These criteria are satisfied in the low magnesium model of epilepsy. Reducing Mg2+ below physiological concentrations or omitting it from artificial cerebrospinal fluid in vitro induces synchronized depolarization shifts in limbic-cortical networks which can be easily recorded extracellularly with a basic electrophysiological set up. These depolarization shifts resemble an increase of the calcium flux into the cell. Multiple depolarizing mechanisms such as NMDA receptor activation or prevention of presynaptic adenosine action converge onto this central pathway. It is hypothized that disturbed calcium homeosthasis is not only a characteristic of epilepsies, but also of affective disorders. Thus, the low magnesium model enables us to screen substances in vitro not only for antiepileptic, but also potential psychiatric use by testing them for calcium antagonistic properties.
Grunze
H
H
Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany.
Walden
J
J
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D000077213:Lamotrigine; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
C107882:7,8-dihydromethysticin; D000927:Anticonvulsants; D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D011743:Pyrimidines; D011753:Pyrones; D014227:Triazines; D002220:Carbamazepine; C043077:ipsapirone; D008274:Magnesium; D002065:Buspirone; D000077213:Lamotrigine; C011889:kavain