The use of Xenopus oocytes to evaluate drugs affecting brain Ca2+ channels: effects of bifemelane and several nootropic agents.
Effects of nootropic or cerebroprotective drugs on voltage-sensitive Ca2+ channels (VSCC) in the mammalian brain were evaluated comparatively by depolarization-evoked Ca2+ channel currents in Xenopus oocytes injected with brain mRNA and by a high K(+)-stimulated 45Ca uptake into synaptosomes. It was found that several anti-amnesic agents (bifemelane, idebenone and vinpocetine) inhibited these VSCC-related responses with stronger potency than phenytoin and flurazepam. On the inhibiting potency of various compounds, there was a significant but weak correlation between the results from synaptosomes and those from the injected oocytes, since nifedipine, verapamil and diltiazem at 100 microM did not reduce 45Ca influx in synaptosomes but partly inhibited VSCCs in the oocytes. The blockade of neuronal L- and N-type VSCCs may participate in the anti-ischemic/hypoxic actions of nootropic drugs.
Kaneko
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Takahashi
H
H
Satoh
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001921:Brain / Q000648:ultrastructure*; D002118:Calcium / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002132:Calcium Radioisotopes; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D011619:Psychotropic Drugs / Q000494:pharmacology; D012333:RNA, Messenger / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D014981:Xenopus
D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D011619:Psychotropic Drugs; D012333:RNA, Messenger; D002118:Calcium; C031906:bifemelane