Van de Heijning B J, Koekkoek-Van den Herik I, Maigret C, Van Wimersma Greidanus T B
Department of Medical Pharmacology, Rudolf Magnus Institute, Utrecht, The Netherlands.
Eur J Pharmacol. 1991 May 17;197(2-3):175-80. doi: 10.1016/0014-2999(91)90518-u.
Naloxone and its congener, methyl naloxone, were given subcutaneously (s.c.) or centrally (i.c.v.) to 24-h water-deprived male rats 30 min prior to decapitation and the effect on plasma levels of vasopressin (VP) and oxytocin (OT) was studied. The potency of s.c. applied methyl naloxone to increase plasma OT levels did not differ from that of naloxone. Injected i.c.v., neither methyl naloxone nor naloxone had a clear effect and they antagonized i.c.v. co-administered dynorphin A-(1-13) equipotently. Methyl naloxone or naloxone, s.c., antagonized the inhibitory action of simultaneous dynorphin A-(1-13) and beta-endorphin-(1-31) given i.c.v., although higher doses of methyl naloxone were required. The data indicate that the sites of inhibition of neurohypophysial hormone release due to beta-endorphin-(1-31) are more likely to be located mostly within the blood-brain barrier, to which methyl naloxone has less ready access, than are the sites of inhibition due to dynorphin A-(1-13).
在断头前30分钟，将纳洛酮及其同系物甲基纳洛酮皮下（s.c.）或脑室内（i.c.v.）给予24小时禁水的雄性大鼠，研究其对血浆中血管加压素（VP）和催产素（OT）水平的影响。皮下注射甲基纳洛酮增加血浆OT水平的效力与纳洛酮无异。脑室内注射时，甲基纳洛酮和纳洛酮均无明显作用，且它们对脑室内共同给予的强啡肽A-（1-13）具有同等的拮抗作用。皮下注射甲基纳洛酮或纳洛酮可拮抗脑室内同时给予的强啡肽A-（1-13）和β-内啡肽-（1-31）的抑制作用，尽管需要更高剂量的甲基纳洛酮。数据表明，与强啡肽A-（1-13）所致的抑制位点相比，β-内啡肽-（1-31）导致神经垂体激素释放受抑制的位点更可能大多位于血脑屏障内，而甲基纳洛酮较难进入该位点。
