摘要：

Most clinically effective antidepressant drugs (ADs) have readily demonstrable effects on the disposition or metabolism of biogenic amines such as norepinephrine, serotonin, and dopamine (1). However, over the past five years, converging lines of evidence indicate that glutamatergic neurotransmission is also affected by ADs (for review see: 2). Furthermore, functional NMDA antagonists (ie. compounds that block or impair activity at the NMDA subtype of glutamate receptor) have been shown to cause AD-like actions (3–8). For example, uncompetitive NMDA antagonists (eg. dizocilpine, memantine) (9,10,7), competitive NMDA antagonists (eg. AP-7, CGP 37849, CGP 39551) (7,11), a polyamine site antagonist (eliprodil) (12), and a glycine partial agonist, 1-aminocyclopropanecarboxylic acid (ACPC), (7,8) all mimic clinically effective agents in preclinical tests (e.g. forced swim and tail suspension) predictive of antidepressant action. Moreover, chronic treatment with dizocilpine, ACPC, and eliprodil downregulate beta-adrenoceptors in rodent cortex (3,6,12), an effect that has sometimes been considered to play an important role in the mechanism of antidepressant action.

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