(iii) Efficacy of ligands for benzodiazepine binding sites (after
infusion of chloroquine)
Three rats were excluded as they died prior to the end of chloroquine
infusion. A further 4 rats died before the end of the experiment but
were included in the study: 1 each from the clonazepam and control
groups, and 2 from the Ro5-4864 group. There was an imbalance in
pre-chloroquine baseline QRS intervals, with higher values in those
randomised to Ro5-4864 compared with other groups. Over 15 minutes,
chloroquine caused significant changes in all cardiovascular parameters
in all randomised groups; however, there was a difference between groups
in the QTc interval, which was shorter in the control versus diazepam,
clonazepam or Ro5-4864 groups. Following the cessation of chloroquine
administration, and administration of randomised treatment, all
parameters rapidly returned to baseline values in all groups (Table 3).
Heart rate was higher, and QTc interval prolonged in both the diazepam
and clonazepam groups, compared with control.