Hough L B, Glick S D, Su K
Pharmacol Biochem Behav. 1986 May;24(5):1257-61. doi: 10.1016/0091-3057(86)90181-4.
The inhibition of hindpaw (non-opiate) footshock-induced analgesia (HP-FSIA) by cimetidine, the histamine H2-receptor antagonist, was characterized in rats, and the drug's presence in brain was demonstrated. Cimetidine (100 mg/kg, IP) inhibited HP-FSIA when administered 30 min before testing, but was inactive when testing began sooner (15 min) or later (1-4 hr) than this time. Lower doses (20 mg/kg) were also ineffective when given 30 min before testing, whereas higher doses (200 mg/kg) effectively inhibited the response. Increasing the footshock current from 4 mA (which elicited cimetidine-sensitive analgesia) to higher currents (5 and 6 mA) yielded cimetidine-insensitive analgesia. Administration of isotopically labeled cimetidine (100 mg/kg, IP, 30 min) yielded whole brain cimetidine levels of 1.95 nmols/g, respectively, with a brain/blood ratio of 0.017. These findings confirm a limited penetration of brain by cimetidine, and show that large peripheral doses of cimetidine are required to block brain H2-receptors. The specific dose and time requirements for cimetidine to inhibit the HP-FSIA are probably attributable to the brain drug levels that can be achieved after peripheral administration.
在大鼠中研究了组胺H2受体拮抗剂西咪替丁对后爪（非阿片类）足底电击诱导镇痛（HP - FSIA）的抑制作用，并证实了该药物在脑中的存在。西咪替丁（100mg/kg，腹腔注射）在测试前30分钟给药时可抑制HP - FSIA，但在测试开始时间早于（15分钟）或晚于（1 - 4小时）这个时间时则无活性。较低剂量（20mg/kg）在测试前30分钟给药时也无效，而较高剂量（200mg/kg）可有效抑制该反应。将足底电击电流从4mA（可引发对西咪替丁敏感的镇痛）增加到更高电流（5mA和6mA）可产生对西咪替丁不敏感的镇痛。给予同位素标记的西咪替丁（100mg/kg，腹腔注射，30分钟）后，全脑西咪替丁水平分别为1.95nmol/g，脑/血比为0.017。这些发现证实西咪替丁对脑的渗透有限，并表明需要大剂量外周给药的西咪替丁才能阻断脑H2受体。西咪替丁抑制HP - FSIA的特定剂量和时间要求可能归因于外周给药后可达到的脑内药物水平。
