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The group of drugs described as "Ca2+-entry blockers" is chemically and pharmacologically heterogeneous. It is believed now that these drugs are useful in the treatment of ischemic disease. In an effort to define which drugs could offer the best therapeutic alternative, a comparative pharmacological study was made. Nine drugs (D-600, diltiazem, flunarizine, nicardipine, nifedipine, nimodipine, nitrendipine, verapamil, tiapamil) were tested in experimental screening models of brain hypoxia, ischemia, cellular intoxication and against bicuculline-induced seizures. Three types of activity were found. Verapamil, D-600, tiapamil and diltiazem were almost inactive, possibly due to their poor brain penetration. The dihydropyridines had a broad spectrum of activity, but considerable differences between these compounds exist. They all were active against hypoxia and less active against ischemia. Out of this subgroup, only nicardipine protected against metabolic intoxication and nifedipine and nicardipine could block seizure components at very high doses. Flunarizine was the only compound with a dose-related effect in all the tests. These results suggested that this combination of screening tests could be used to find compounds with an interesting activity in the field of cerebral protection.

“Calcium Entry Blockers” as Cerebral Protecting Agents: Comparative Activity in Tests of Hypoxia and Hyperexcitability