Porsius A J, Borgdorff P, van Rooij H H, de Neef J H
Arch Int Pharmacodyn Ther. 1987 Mar;286(1):123-35.
The inhibitory effects of the morphine-like drugs fentanyl, nicomorphine (3,6-dinicotinoyl morphine, Vilan) and its active metabolite 6-nicotinoyl morphine (6-NM) on phrenic nerve activity (PNA) were quantified. Therefore, the drugs were simultaneously infused into the left and right vertebral artery of anaesthetized cats. Previously we demonstrated that drugs, administered via these arteries, accumulate within the pontomedullary region, whereas only insignificant amounts reach higher brain areas and peripheral structures. The results were compared with the effects of i.v. administration. It is shown that fentanyl already inhibits PNA after 60 ng via the vertebral arteries. Nicomorphine and its metabolite have much less influence on respiration (factor 564 and 47, respectively). The difference in potency between nicomorphine and 6-NM was less after i.v. injection, indicating that nicomorphine needs metabolization in order to unfold full biological activity. Haemodynamic parameters are not affected after central administration even when PNA is almost completely depressed. After i.v. injection of relatively high doses, blood pressure falls, but probably not by an interaction with opiate receptors in the lower brain stem, since it could not be reversed by intravertebral naloxone.
对吗啡样药物芬太尼、尼可吗啡（3,6 - 二烟酰吗啡，维兰）及其活性代谢产物6 - 烟酰吗啡（6 - NM）对膈神经活动（PNA）的抑制作用进行了定量研究。为此，将这些药物同时注入麻醉猫的左右椎动脉。此前我们证明，通过这些动脉给药的药物会在脑桥延髓区域蓄积，而仅有微量药物会到达更高的脑区和外周结构。将结果与静脉注射给药的效果进行了比较。结果显示，通过椎动脉给药时，芬太尼在剂量达到60纳克后就已开始抑制PNA。尼可吗啡及其代谢产物对呼吸的影响要小得多（分别为564倍和47倍）。静脉注射后，尼可吗啡与6 - NM之间的效价差异较小，这表明尼可吗啡需要代谢才能发挥全部生物活性。即使PNA几乎完全被抑制，中枢给药后血流动力学参数也不受影响。静脉注射相对高剂量药物后，血压会下降，但这可能并非通过与脑干下部的阿片受体相互作用所致，因为椎内注射纳洛酮无法使其逆转。
