Kasama T, Fujii Y, Aida Y, Mayuzumi K, Mayuzumi Y, Goto M, Gomita Y, Moriyama M, Ichimaru Y
Nihon Yakurigaku Zasshi. 1983 Feb;81(2):149-65.
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.
在小鼠和大鼠中研究了口服和直肠给药的溴西泮药理作用之间的差异。1）两种给药途径下，溴西泮均剂量依赖性地延长了硫喷妥钠、乙醇和乙醚诱导的睡眠时间。2）通过热板法和痛觉测定试验确认了溴西泮的镇痛作用。在热板试验中，两种途径给予0.5mg/kg剂量的溴西泮均增强了吗啡和喷他佐辛的镇痛作用。3）在倾斜屏幕试验和转棒试验中，直肠给药的溴西泮肌肉松弛作用比口服给药更强。直肠给药的溴西泮这种作用约为口服给药的2倍。4）溴西泮抑制最大电击、戊四氮和印防己毒素诱导的惊厥。在戊四氮诱导的惊厥中，直肠给药的溴西泮抑制作用为口服给药的2倍。在其他惊厥试验中，口服和直肠给药之间未发现显著差异。5）双侧嗅球切除大鼠（OB大鼠）的过度情绪化和杀鼠行为（杀鼠行为）通过口服和直肠给予溴西泮呈剂量依赖性降低。直肠给药的效果比口服给药更强。溴西泮的效力约为相同途径给予地西泮的20倍。直肠给予溴西泮可抑制遭受足部电击的小鼠的打斗行为，且该效果与口服给药相同。6）在斯金纳箱的下丘脑外侧自我刺激试验中，直肠给予0.2mg/kg溴西泮显著增加了杠杆按压反应率。7）仅直肠给予5mg/kg剂量的溴西泮可显著抑制甲基苯丙胺诱导的小鼠多动。8）溴西泮对正常大鼠体温的降低作用在两种给药途径中相同且呈剂量依赖性。从这些数据可知，口服和直肠给药的溴西泮在作用持续时间和部分效力方面存在显著的药理作用差异；因此，直肠给药的溴西泮可能是一种有用的临床剂型。
