Rationale for maintenance pharmacotherapy of opiate dependence.
Rationale for maintenance pharmacotherapy of opiate dependence.
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发表时间：
1992
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通讯作者：
M. Kreek
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作者：
M. Kreek
此时，距开始开发用于阿片成瘾维持治疗的美沙酮的初步研究 27 年后，结果表明[表；见正文] 美沙酮符合用于长期治疗成瘾的药物的大多数标准。口服后有效：在人体中生物半衰期长，长期治疗时副作用极小，没有真正的毒作用或严重副作用。此外，美沙酮已被证明在将药物治疗与“无药物”治疗的最佳要素（即咨询和心理支持）相结合的方案中适当使用时非常有效。除了药物治疗外，还应根据需要获得（如果不是现场）医疗和行为护理，以及与康复各个方面的资源的联系。目前，在临床前和临床水平上，通过科学实验已经确定了用于慢性阿片成瘾治疗的美沙酮的许多作用、具体作用位点和作用机制。众所周知，美沙酮可以预防戒断症状，防止药物饥饿或药物渴望，阻止其他阿片类药物的欣快感，并防止非法使用阿片类药物的复发。已知美沙酮的作用位点位于特定的阿片受体。迄今为止的研究表明，在长期阿片激动剂灌注过程中，阿片受体没有明显的下调或上调，尽管长期施用阿片拮抗剂纳曲酮似乎确实上调阿片受体。临床研究表明，长期使用美沙酮可以使内源性阿片类药物之一、β-内啡肽以及人类垂体前叶释放和加工的 POMC 衍生的相关肽的释放和外周水平正常化。在长期维持治疗期间，脑脊液中的 β-内啡肽水平也变得正常，这反映了 POMC 产生的大脑或下丘脑部位的 β-内啡肽的加工和释放明显正常。 β-内啡肽研究的现有数据表明，有一个[表；与间歇性给药然后突然戒断海洛因等短效阿片类药物相比，美沙酮稳态给药期间内源性阿片类药物系统总体上正常化，而不是破坏。尽管关于阿片成瘾的神经生物学还有很多东西有待了解，但目前我们确实对阿片和阿片类药物的影响了解很多。（摘要截断为 400 字）
At this time, 27 years after the initial studies on development of methadone for the maintenance treatment of opiate addiction were begun, it has been shown that [table; see text] methadone meets most criteria for a pharmacologic agent for chronic treatment of an addiction. It is effective after oral dosing: it has a long biological half-life in humans, it causes minimal side effects when used in chronic treatment, and it has no true toxic effects or serious side effects. Also methadone has been shown to be very effective when appropriately used in programs which combine pharmacotherapy with the best elements of "drug free" treatment, that is, counseling and psychological support. In addition to pharmacological treatment, there should be access to, if not on-site, medical and behavioral care as needed, as well as linkage to resources for various aspects of rehabilitation. At this time many of the actions, as well as the specific sites of action, and mechanisms of actions of methadone as used in chronic treatment of opiate addiction have been defined by scientific experimentation, both at the preclinical and clinical levels. It is known that methadone prevents abstinence symptoms, prevents drug hunger or craving, blocks euphorogenic effects of other opiates, and prevents relapse to illicit use of opiates. It is known that the site of action of methadone is at specific opioid receptors. Research to date suggests that there is no demonstrable down-regulation or up-regulation of opioid receptors during chronic opioid agonist perfusion, although chronic administration of the opioid antagonist naltrexone does appear to up-regulate opioid receptors. Clinical studies show that chronic use of methadone allows normalization of release and peripheral levels of one of the classes of endogenous opioids, beta-endorphin, and the related peptides derived from POMC released and processed from the anterior pituitary in humans. Also levels of beta-endorphin in cerebrospinal fluid become normal during chronic maintenance treatment, reflecting apparently normal processing and release of beta-endorphin at brain or hypothalamic sites of POMC production. Available data from studies of beta-endorphin indicate that there is a [table; see text] normalization, rather than disruption, of the endogenous opioid system in general during steady state administration of methadone, as contrasted with intermittent dosing and then abrupt withdrawal of short-acting opiates such as heroin. Although there is still much to be learned about the neurobiology of opiate addiction, at this time we do know a great deal about the effects of opiates and opioids.(ABSTRACT TRUNCATED AT 400 WORDS)