Kim S, Wagner H N, Villemagne V L, Kao P F, Dannals R F, Ravert H T, Joh T, Dixon R B, Civelek A C
Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2179, USA.
J Nucl Med. 1997 Nov;38(11):1726-31.
Surgical procedures usually involve the administration of narcotic drugs as anesthetics or adjuvants. To reverse the effects of anesthesia, opioid antagonists such as naloxone are commonly used. Due to its short lasting effects, patients receiving naloxone must be monitored carefully. Nalmefene, a pure opiate antagonist with a longer duration of action than naloxone, has shown promise in the reversal of opioid anesthesia.
A simple dual-detector positron radiation detector system and [11C]carfentanil were used to compare the duration of blockade of cerebral mu opioid receptors by naloxone and nalmefene in eight normal volunteers. Carbon-11-carfentanil brain kinetics were monitored for 5 min and 2, 4, 8 and 24 hr after the administration of either nalmefene (1 mg or 1 microg/kg) or naloxone (2 mg or 2 microg/kg). Blood samples were obtained at the same times for plasma determinations.
Clearance half-times from opioid receptors were 28.7 +/- 5.9 hr for 1 mg of nalmefene and 2.0 +/- 1.6 hr for 2 mg of naloxone. Brain clearance times were about 21.1 and 3.4 times slower than plasma clearance times for nalmefene and naloxone, respectively.
These findings suggest that the prolonged effects of nalmefene are related to the slow dissociation of nalmefene from opioid receptors, which are not reflected in the plasma curve. This longer blockade of opioid receptors by nalmefene represents an advantage in the clinical management of postsurgical reversal of narcotic anesthesia and opioid side effects as well as the reversal of opioid overdose.
外科手术通常需要使用麻醉药品作为麻醉剂或辅助剂。为了逆转麻醉效果，常用纳洛酮等阿片类拮抗剂。由于其作用持续时间短，接受纳洛酮治疗的患者必须密切监测。纳美芬是一种纯阿片类拮抗剂，作用持续时间比纳洛酮长，在逆转阿片类麻醉方面已显示出前景。
使用一个简单的双探测器正电子辐射探测系统和[11C]卡芬太尼，比较纳美芬和纳洛酮对8名正常志愿者脑μ阿片受体的阻断持续时间。在给予纳美芬（1mg或1μg/kg）或纳洛酮（2mg或2μg/kg）后，监测5分钟以及2、4、8和24小时的碳-11-卡芬太尼脑动力学。同时采集血样进行血浆测定。
1mg纳美芬从阿片受体的清除半衰期为28.7±5.9小时，2mg纳洛酮为2.0±1.6小时。纳美芬和纳洛酮的脑清除时间分别比血浆清除时间慢约21.1倍和3.4倍。
这些发现表明，纳美芬作用时间延长与纳美芬从阿片受体缓慢解离有关，这在血浆曲线中未得到体现。纳美芬对阿片受体较长时间的阻断在术后逆转麻醉、阿片类副作用以及逆转阿片类药物过量的临床管理中具有优势。
