Experimental protocol
In developing a model of experimental toxicity, animals (6 per group) were allocated at random to different doses of chloroquine diphosphate dissolved in 0.9% w/v NaCl. Non-ventilated rats were randomised to intravenously infused doses (calculated as chloroquine base) of 0.5, 1, 2 or 4 mg kg-1 min-1; ventilated rats 1, 2, or 4 mg kg-1 min-1; and rabbits 0.5, 1 or 2 mg kg-1 min-1for a maximum period of 60 minutes or until death, after an initial period of stabilisation of at least 20 minutes.
Six interventional randomised controlled trials were subsequently conducted to assess the efficacy of diazepam, clonazepam and Ro5-4864: (i) prior, (ii) during and (iii) after chloroquine intoxication (Table 1); and the effects of diazepam: (iv) in high dose, (v) in non-barbiturate anaesthetised rats, and (vi) co-administered with adrenaline. Six rats were randomised to each intervention group within each of these studies. Benzodiazepines (and vehicles) were administered as a slow intravenous bolus over 2 minutes.