MRI of entorhinal cortex in mild Alzheimer's disease
MRI of entorhinal cortex in mild Alzheimer's disease
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DOI：
10.1016/s0140-6736(05)74869-8
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发表时间：
1999-01-02
期刊：
影响因子：
168.9
通讯作者：
Wisniewski, HM
中科院分区：
文献类型：
--
作者：
Bobinski, M;de Leon, MJ;Wisniewski, HM
芬特明已被用于在美国治疗肥胖，因为至少1961年，并广泛使用后，1992年与芬氟拉明组合。1997年的一项研究表明，这种组合可能与心脏瓣膜疾病有关，类似于在类癌综合征或服用麦角胺的患者中所见，以及与肺动脉高压有关，如前所述。1有人认为，这些发现是由于循环5-羟色胺增加。随后，美国食品和药物管理局在服用芬氟拉明而不服用芬特明的患者中发现了心脏瓣膜病变。由于缺乏关于芬特明作用的数据，我们确定芬特明是否可以改变交感神经元释放的去甲肾上腺素以外的其他单胺的代谢。在大鼠中，芬特明，像d-安非他明一样，释放多巴胺进入大脑突触。2我们测试了低剂量（口服15 mg）对人类血浆多巴胺的影响。9名年轻的非肥胖男性志愿者在接受药物前和接受药物后1、2或4小时抽血。用放射免疫测定法测定血浆多巴胺浓度，芬特明升高（p<0.05;方差分析; Wilcoxon检验）;然而，用ELISA测定血小板内血清素水平增加更大，并经高效液相色谱法证实（r= 0.496; p<0.001）。血小板5-羟色胺含量的增加可能反映肠嗜铬细胞5-羟色胺释放增加或单胺氧化酶（MAO）抑制其代谢。血浆5-羟色胺浓度轻微下降的发现表明，这种增加是由于MAO抑制而不是5-羟色胺释放增加所致。在20世纪70年代早期，芬特明抑制分解5-羟色胺的单胺氧化酶是众所周知的，但显然这一信息从未出现在药物标签上。有证据表明，游离血浆5-羟色胺可损害血管组织5，并且其浓度通常通过两个高容量系统的作用保持在较低水平，这两个系统将其从循环中去除-吸收到血小板和MAO中。如果芬氟拉明和芬特明方案确实产生了肺动脉高压和心脏瓣膜病变，那么如果美国境内的芬特明标签提到该药物是一种MAO抑制剂，那么它们可能已经被消除。这样的提及也会警告医生不要将芬特明与氟西汀，氟苯丙胺或其他SSRI联合使用。
Phentermine has been used in the USA to treat obesity since at least 1961 and was widely used after 1992 in combination with fenfluramine. A study in 1997 suggested that this combination could be associated with heart-valve disease similar to that seen in the carcinoid syndrome or in patients who had taken ergotamine, as well as with pulmonary hypertension, previously described. 1 It was suggested that these findings, were due to an increase in circulating serotonin. Subsequently, the US Food and Drug Administration found heart-valve lesions among patients taking a fenfluramine without phentermine. Given the paucity of data on phentermine’s actions, we determined whether phentermine could modify the metabolism of other monoamines besides the norepinephrine released from sympathetic neurons. In rats, phentermine, like d-amphetamine, releases dopamine into brain synapses. 2 We tested the ability of a low dose (15 mg by mouth) to affect plasma dopamine in human beings. Nine young, non-obese male volunteers gave blood just before, and 1, 2, or 4 h after receiving the drug. Plasma dopamine concentrations, assayed by radioimmunoassay3, rose with phentermine (p< 0· 05; ANOVA; Wilcoxon’s test); however a greater increase was noted in serotin levels within the blood platelets as assayed by ELISA and confirmed by high performance liquid chromatography (r= 0· 496; p< 0· 001). The increase in platelet serotonin could reflect increased release of serotonin from enterochromaffin cells, or inhibition of its metabolism by monoamine oxidase (MAO). That the increase resulted from MAO inhibition and not from increased serotonin release was shown by the finding that plasma serotonin concentration fell slightly. That phentermine inhibits the MAO which catabolises serotonin was well known in the early 1970s, 4 but apparently this information never made its way onto the drug’s label. There is evidence that free plasma serotonin can damage vascular tissue5 and that its concentration is normally kept low by the action of the two high-capacity systems that remove it from the circulation—uptake into platelets and MAO. If the fenfluramine and phentermine regimen did produce pulmonary hypertension and cardiac valve lesions then they might have been obviated had the phetermine label within the US mentioned that the drug is an MAO inhibitor. Such a mention would also warn physicians against combining phentermine with fluoxetine, flenfluramine, or other SSRIs.