Sambunaris A, Hesselink J K, Pinder R, Panagides J, Stahl S M
Department of CNS Research, Solvay Pharmaceuticals, Marietta, Ga., USA.
J Clin Psychiatry. 1997;58 Suppl 6:40-53.
A large number of novel antidepressants acting on a variety of neurotransmitter receptors are currently undergoing clinical evaluation. Most agents have a dual mechanism of action on two or more neurotransmitter receptors, including two serotonin receptors, two noradrenergic receptors, or a combination of serotonin and noradrenergic mechanisms. The most recently approved agent, mirtazapine, is an example of this approach of simultaneously targeting both the serotonergic and noradrenergic systems. Specifically, mirtazapine's alpha 2 antagonism disinhibits both serotonin and norepinephrine neurotransmission while its serotonin-2 and serotonin-3 antagonist properties reduce the side effects normally associated with nonselective serotonin receptor activation by serotonin selective reuptake inhibitors (SSRIs). This approach of "designer polypharmacy" applies principles of rational pharmacologic combinations to enhance efficacy and improve tolerability of the new and emerging antidepressants.
目前，大量作用于多种神经递质受体的新型抗抑郁药正在进行临床评估。大多数药物对两种或更多神经递质受体具有双重作用机制，包括两种血清素受体、两种去甲肾上腺素能受体，或血清素和去甲肾上腺素能机制的组合。最近获批的药物米氮平就是同时靶向血清素能和去甲肾上腺素能系统这种方法的一个例子。具体而言，米氮平的α2拮抗作用解除了血清素和去甲肾上腺素神经传递的抑制，而其血清素-2和血清素-3拮抗特性减少了通常与血清素选择性再摄取抑制剂（SSRI）非选择性激活血清素受体相关的副作用。这种“设计型复方药物”方法应用了合理药物组合的原则，以提高新型抗抑郁药的疗效并改善其耐受性。
