Pharmacological characterisation of the thermogenic effect of bupropion.
Pharmacological characterisation of the thermogenic effect of bupropion.
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安非他酮生热作用的药理学特征。
DOI：
10.1016/j.ejphar.2004.07.004
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发表时间：
2004
影响因子：
5
通讯作者：
M. Stock
中科院分区：
文献类型：
--
作者：
Y. Liu;I. Connoley;D. Heal;M. Stock
通过测量热中性（29°C）下的耗氧量，在雌性 Wistar 大鼠中研究了安非他酮生热效应的药理学机制。安非他酮 (30 mg/kg) 迅速增加耗氧量 (VO2)，并在 30 分钟时达到最大效果，并且 VO2 在整个 4 小时实验期间保持升高状态。非选择性 5-羟色胺（5-HT 或血清素）受体拮抗剂麦角林 (1 mg/kg) 和 α1-肾上腺素受体拮抗剂哌唑嗪 (1 mg/kg) 对安非他酮的 VO2 反应没有影响，而 α2-肾上腺素受体拮抗剂 RS79948 [(8aR, 12aS, 13aS)-5,8,8a,9,10,11,12,12a,13,13a-十氢-3-甲氧基-12-(乙基磺酰基)-6H-异喹啉[2,1-g][1,6]-萘啶盐酸盐](1 mg/kg)，增强了响应。高剂量的非选择性 β-肾上腺素受体拮抗剂普萘洛尔 (20 mg/kg) 可显着抑制前 60 分钟内对安非他酮的 VO2 反应，但低剂量 (1 mg/kg) 则没有影响。用多巴胺 D2/D1 受体拮抗剂 (+)butaclamol (200 μg/kg) 进行预处理，在前 60 分钟内对安非他酮的 VO2 反应产生部分但显着的抑制 (P<0.01)，并且该拮抗剂在 90 至 240 分钟之间消除了安非他酮的作用。使用高剂量普萘洛尔 (20 mg/kg) 和 (+)butaclamol (200 μg/kg) 组合进行预处理可防止安非他酮引起的 VO2 增加。结论是β3-肾上腺素受体亚型以及多巴胺D2/D1受体是安非他酮引起的耗氧量增加的原因。我们之前已经证明安非他酮不会显着减少大鼠的食物摄入量。因此，在该物种中，其减肥作用主要来自通过激活 β3-肾上腺素能和多巴胺 D2/D1 受体介导的生热作用。由于临床上也有报道称安非他酮不会改变食物摄入量，因此生热作用也可能有助于其对人体的抗肥胖作用。
The pharmacological mechanism of bupropion's thermogenic effect has been investigated in female Wistar rats by measuring oxygen consumption at thermoneutrality (29 °C). Bupropion (30 mg/kg) rapidly increased oxygen consumption (VO2) with a maximum effect at 30 min, and VO2remained elevated throughout the 4-h experimental period. The nonselective 5-hydroxytryptamine (5-HT or serotonin) receptor antagonist, metergoline (1 mg/kg), and the α1-adrenoceptor antagonist, prazosin (1 mg/kg), had no effect on the VO2response to bupropion, whereas the α2-adrenoceptor antagonist, RS79948 [(8aR, 12aS, 13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]-naphthyridine hydrochloride] (1 mg/kg), potentiated the response. The VO2response to bupropion during the first 60 min was significantly inhibited by a high dose of the nonselective β-adrenoceptor antagonist, propranolol (20 mg/kg), but it had no effect at a low dose (1 mg/kg). Pretreatment with the dopamine D2/D1 receptor antagonist, (+)butaclamol (200 μg/kg), caused a partial, but significant, inhibition (P<0.01) of the VO2response to bupropion during the first 60 min, and this antagonist abolished the effect of bupropion between 90 and 240 min. Pretreatment with a combination of a high dose of propranolol (20 mg/kg) and (+)butaclamol (200 μg/kg) prevented any increase in VO2induced by bupropion. It is concluded that the β3-adrenoceptor subtype, as well as dopamine D2/D1 receptors, is responsible for the increase in oxygen consumption induced by bupropion. We have previously demonstrated that bupropion did not significantly reduce food intake in rats. Hence, in this species, its weight-reducing action predominantly results from thermogenesis mediated via activation of β3-adrenergic and dopamine D2/D1 receptors. Because bupropion has also been reported not to alter food intake in the clinic, thermogenesis may also contribute to its antiobesity effect in man.