Pircio A W, Gylys J A
J Pharmacol Exp Ther. 1975 Apr;193(1):23-34.
Oxilorphan is a fully synthetic morphinan derivative containing the 14-hydroxy group characteristics of naloxone and naltrexone. As a narcotic antagonist, oxilorphan was 4 times more potent than dl-cyclazocine, equipotent to naloxone and about one-fourth as potent as naltrexone parenterally. Duration studies in rodents were inconclusive, but in antagonism of morphine analgesia and miosis in the dog, oxilorphan was longer acting than naloxone and equivalent to dl-cyclazocine. Oxilorphan was inactive in the conventional animal thermal analgesic tests. However, oxilone did exhibit relatively weak analgesic activity in preventing phenylquinone-induced abdominal contraction at doses about 700 times higher than those required for antagonist activity. The analgesic potency of oxilorphan was only 120 and 1/300 the potency of morphine and dl-cyclazocine, respectively, but was significantly greater than naltrexone and naloxone. Mice chronically treated with increasing doses of oxilorphan failed to exhibit withdrawal jumping after naloxone challenge. General central nervous system activity studies showed oxilorphan to be relatively free from central side effects at doses at which dl-cyclazocine produced pronounced effects.
氧吗啡酮是一种完全合成的吗啡喃衍生物，具有纳洛酮和纳曲酮的14-羟基特征。作为一种麻醉拮抗剂，氧吗啡酮的效力比消旋环唑辛强4倍，与纳洛酮相当，胃肠外给药时效力约为纳曲酮的四分之一。对啮齿动物的持续时间研究尚无定论，但在拮抗犬的吗啡镇痛和瞳孔缩小时，氧吗啡酮的作用时间比纳洛酮长，与消旋环唑辛相当。氧吗啡酮在传统的动物热镇痛试验中无活性。然而，氧吗啡酮在预防苯醌诱导的腹部收缩方面确实表现出相对较弱的镇痛活性，其剂量比拮抗活性所需剂量高约700倍。氧吗啡酮的镇痛效力分别仅为吗啡和消旋环唑辛的1/20和1/300，但明显大于纳曲酮和纳洛酮。用递增剂量的氧吗啡酮长期治疗的小鼠在接受纳洛酮激发后未出现戒断跳跃。一般中枢神经系统活性研究表明，在消旋环唑辛产生明显作用的剂量下，氧吗啡酮相对没有中枢副作用。
