title: Calcium antagonists can be classified using in vitro toxicity and potency indices.
abstract: The toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage-operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate an in vitro therapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that the in vitro therapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compounds.
authors.affiliation: Riom Laboratoires CERM, France.
authors.forename: R
authors.initials: R
authors.lastname: Shrivastava
authors.forename: G
authors.initials: G
authors.lastname: John
authors.forename: R
authors.initials: R
authors.lastname: Massingham
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000145:classification* / Q000494:pharmacology / Q000633:toxicity; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers