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.