Differences between the pharmacological effects of
bromazepam given by oral and
rectal administration were investigated in mice and rats. 1)
Bromazepam dose-dependently prolonged the sleeping time induced by
thiopental-Na,
ethanol and
ether by both administration routes. 2) The
analgesic action of
bromazepam was recognized by the hot-plate method and the algolytic test. In the hot-plate test,
analgesic actions of
morphine and
pentazocine were potentiated by
bromazepam in a dose of 0.5 mg/kg by both routes. 3) The muscle relaxant effect of
bromazepam administered rectally was more potent than that administered orally in the inclined screen test and the rotarod test. This effect of
bromazepam by
rectal administration was approximately 2 times as potent as that by
oral administration. 4)
Bromazepam inhibited the convulsion induced by maximum electric
shock,
pentylenetetrazol and
picrotoxin. In
pentylenetetrazol-induced convulsion, the inhibitory effect of
bromazepam administered rectally was 2 times as potent as that administered orally. In the other convulsion test, no significant differences between oral and
rectal administration could be recognized. 5) Hyperemotionality and muricide (mouse-killing behaviour) of rats with bilateral olfactory bulb ablations (OB rat) were reduced by oral and
rectal administrations of
bromazepam in a dose-dependent manner. The effects by
rectal administration were more potent than that by
oral administration.
Bromazepam was approximately 20 times as potent as
diazepam administered by the same route. Fighting behaviour in mice subjected to footshock was suppressed by
rectal administration of
bromazepam, and this effect was as same as that by
oral administration. 6) The rate of lever pressing response in the lateral hypothalamic self-stimulation test in the Skinner box was markedly increased by
rectal administration of 0.2 mg/kg
bromazepam. 7)
Methamphetamine-induced hyperactivity of mice was significantly suppressed only by
bromazepam administered rectally in a dose of 5 mg/kg. 8) The falling effect of
bromazepam on body temperature in normal rats was the same in both administration routes and was dose-dependent. From these data, significant differences of the pharmacological effects between oral and
rectal administration of
bromazepam were recognized in the duration of action and, in part, potencies; and therefore,
rectal administration of
bromazepam may be a useful
dosage form for clinical use.