Luscombe G P, Hopcroft R H, Thomas P C, Buckett W R
Research Department, Boots Company PLC, Nottingham, U.K.
Neuropharmacology. 1989 Feb;28(2):129-34. doi: 10.1016/0028-3908(89)90048-8.
Sibutramine HCl is an inhibitor of the reuptake of monoamines with a pharmacological profile in rodents indicative of antidepressant activity. The secondary (BTS 54 354) and primary (BTS 54 505) amine metabolites of the tertiary amine sibutramine HCl exhibit similar in vivo pharmacological activity to the parent compound. Thus, each compound displays potent activity in acute behavioural models predictive of antidepressant effects and a comparable ability to inhibit the uptake of monoamines in vivo. In addition, BTS 54 354 and BTS 54 505 induce an equally rapid and potent down-regulation of cortical beta-adrenoceptors in the rat as sibutramine HCl. The secondary and primary amines are, however, considerably more active than sibutramine HCl as inhibitors of the uptake of noradrenaline, dopamine and 5-hydroxytryptamine in vitro. The potent inhibition of the reuptake of noradrenaline by the secondary and primary amine metabolites probably contributes to the rapid and potent down-regulation of beta-adrenoceptors in the rat, induced by the putative antidepressant sibutramine HCl.
盐酸西布曲明是一种单胺再摄取抑制剂，在啮齿动物中的药理学特征表明其具有抗抑郁活性。叔胺盐酸西布曲明的二级（BTS 54 354）和一级（BTS 54 505）胺代谢物在体内表现出与母体化合物相似的药理活性。因此，每种化合物在预测抗抑郁作用的急性行为模型中均显示出强效活性，并且在体内抑制单胺摄取的能力相当。此外，与盐酸西布曲明一样，BTS 54 354和BTS 54 505在大鼠中诱导皮质β-肾上腺素能受体同样快速且强效的下调。然而，二级和一级胺作为去甲肾上腺素、多巴胺和5-羟色胺体外摄取抑制剂比盐酸西布曲明活性强得多。二级和一级胺代谢物对去甲肾上腺素再摄取的强效抑制可能促成了推测的抗抑郁药盐酸西布曲明在大鼠中诱导的β-肾上腺素能受体快速且强效的下调。
