The Novel Development of an Experimental Model of Dihydropyridine Calcium Channel Blocker Poisoning using Intravenous Amlodipine

BACKGROUND: Cardiovascular drug poisoning remains a leading cause of fatality. Within this class, calcium channel blockers (CCBs) account for the majority of deaths. CCBs are typically categorized as dihydropyridines (i.e. amlodipine or nifedipine) versus the non-dihydropyridine (i.e. verapamil and diltiazem) which are the most potent and once considered the CCB type responsible for all CCB-related deaths. Most recently, dihydropyridine deaths have increased. While there are established models of nondihydropyridine poisoning there currently are no established experimental models of dihydropyridine poisoning. METHODS: Electrocardiogram electrodes and intravenous lines were placed in anesthetized Spraque-Dawley rats. Various doses of amlodipine were administrated as a constant infusion to mimic continued gastrointestinal absorption. Intravenous amlodipine dosing was determined by the Dixon "up-and-down" method. Animals were observed for a total of two hours and death or survival was recorded. RESULTS: Various solvents were used such as tween and ethanol. Amlodipine was successfully dissolved in 20% DMSO. The maximum likelihood estimate for LD50 was 8.65 mg/kg (SE, +/- 2.67 mg/kg). CONCLUSIONS: A reliable experimental model of dihydropyridine poisoning using intravenous amlodipine is presented which will allow future studies concerning pathophysiology of shock from dihydropyridine poisoning and treatment.