Sasaki K, Furusawa S, Takayanagi G
J Pharmacobiodyn. 1981 Jun;4(6):394-401. doi: 10.1248/bpb1978.4.394.
The effect of doxapram, a respiratory stimulant, on the pentobarbital sleeping time was investigated in mice. The sleeping time induced by the intraperitoneal injection of pentobarbital was prolonged 0--120 min after the administration of doxapram (25-100 mg/kg, i.p.). The pretreatment with doxapram 60 min before had no effect on the anesthetic time induced by ether and on the sleeping time induced by the intracerebroventricular injection of pentobarbital, while increased the lethality of pentobarbital only slightly and the levels of pentobarbital in the plasma and brain significantly. The activities of pentobarbital oxidase and aminopyrine N-demethylase in the 9000 X g supernatant fraction of the liver were inhibited by the pretreatment with doxapram 60 min before the test. On the other hand, 12-24 hr after the injection of doxapram the pentobarbital sleeping time was markedly shortened. Thus, the biphasic effect of doxapram, prolongation at first and shortening later, on the pentobarbital sleeping time was observed. It is possible that doxapram inhibits the hepatic microsomal drug-metabolizing enzymes without an increase in the sensitivity of the central nervous system at first and stimulates these enzymes during the second phase.
在小鼠中研究了呼吸兴奋剂多沙普仑对戊巴比妥睡眠时间的影响。腹腔注射戊巴比妥诱导的睡眠时间在给予多沙普仑（25 - 100毫克/千克，腹腔注射）后延长了0 - 120分钟。提前60分钟用多沙普仑预处理对乙醚诱导的麻醉时间和脑室内注射戊巴比妥诱导的睡眠时间没有影响，而仅略微增加了戊巴比妥的致死率，并显著提高了血浆和脑中戊巴比妥的水平。在试验前60分钟用多沙普仑预处理可抑制肝脏9000×g上清液部分中戊巴比妥氧化酶和氨基比林N - 脱甲基酶的活性。另一方面，注射多沙普仑12 - 24小时后，戊巴比妥睡眠时间明显缩短。因此，观察到多沙普仑对戊巴比妥睡眠时间具有双相作用，先是延长，随后缩短。多沙普仑可能首先抑制肝微粒体药物代谢酶而不增加中枢神经系统的敏感性，在第二阶段刺激这些酶。
