Tortella F C, Cowan A, Adler M W
Neuropharmacology. 1984 Jul;23(7A):749-54. doi: 10.1016/0028-3908(84)90107-2.
The influence of centrally administered meperidine, normeperidine and pentazocine on the excitability of brain was studied by measuring the threshold for flurothyl-induced convulsions in rats. All three opioids are reported to lower seizure thresholds when given subcutaneously to rats in this test. Dose-and time-dependent changes in the seizure threshold occurred after intracerebroventricular injection of pentazocine (10-160 micrograms), meperidine (25-150 micrograms) and normeperidine (50-150 micrograms). Rapid increases in the seizure threshold were associated with pentazocine and meperidine, whereas a slowly developing decrease in the threshold was caused by normeperidine. Naloxone (10 mg/kg, s.c.) antagonized the anticonvulsant effect of meperidine (but not that of pentazocine) and enhanced the proconvulsant effect of normeperidine. Thebaine (25-150 micrograms), which had no marked influence on the seizure threshold when given intracerebroventricularly, lowered the threshold after subcutaneous injection of 12.5 and 25 mg/kg. This effect was not altered by injection of naloxone. These results show that centrally administered opioids can act on excitatory or inhibitory systems that regulate seizure mechanisms in the rat brain. Furthermore both naloxone-sensitive and naloxone-insensitive components are involved. Meperidine, pentazocine and thebaine have different actions on the seizure threshold after intracerebroventricular, as opposed to subcutaneous, administration. This work has, therefore, identified the route of administration as a critical variable in the effect of opioids on the seizure threshold in rats.
通过测量氟烷诱发大鼠惊厥的阈值，研究了脑室内注射哌替啶、去甲哌替啶和喷他佐辛对大鼠脑兴奋性的影响。据报道，在该试验中，给大鼠皮下注射这三种阿片类药物均会降低惊厥阈值。脑室内注射喷他佐辛（10 - 160微克）、哌替啶（25 - 150微克）和去甲哌替啶（50 - 150微克）后，惊厥阈值出现剂量和时间依赖性变化。喷他佐辛和哌替啶使惊厥阈值迅速升高，而去甲哌替啶则导致阈值缓慢下降。纳洛酮（10毫克/千克，皮下注射）拮抗哌替啶的抗惊厥作用（但不拮抗喷他佐辛的），并增强去甲哌替啶的促惊厥作用。脑室内注射蒂巴因（25 - 150微克）时对惊厥阈值无明显影响，但皮下注射12.5和25毫克/千克后会降低阈值。注射纳洛酮不会改变这种作用。这些结果表明，脑室内注射阿片类药物可作用于调节大鼠脑惊厥机制的兴奋性或抑制性系统。此外，涉及纳洛酮敏感和不敏感成分。与皮下注射相比，脑室内注射时哌替啶、喷他佐辛和蒂巴因对惊厥阈值有不同作用。因此，这项研究确定给药途径是阿片类药物对大鼠惊厥阈值影响的关键变量。
