Bradford L D, Tulp M T, Schipper J
Arch Int Pharmacodyn Ther. 1987 Jun;287(2):188-202.
Clovoxamine, a nontricyclic antidepressant, has a dual action in blocking the reuptake of both noradrenaline and serotonin. Acute in vitro receptor binding studies showed that clovoxamine has little affinity for muscarinic, histaminergic, serotonergic and adrenergic binding sites. After chronic administration, clovoxamine induced a decrease in the functional beta-adrenergic receptor coupled c-AMP response. A comparison made between clovoxamine (with a very short half life value in rats) and desipramine indicated that the decrease in the beta-receptor coupled c-AMP response was similar, regardless whether the compounds were injected i.p. twice daily (10 mg/kg) or delivered via an osmotic minipump (20 mg/kg/day) for 21 days. Chronic administration of both clovoxamine and desipramine by twice daily i.p. injections or osmotic minipumps in rats resulted also in a down regulation of the number of 5-HT2 receptors in frontal cortex. The alteration in beta-receptor number (Bmax) did not correlate with the decrease in adenylate cyclase activity. These data support a multistep process of the down regulation of the beta-adrenergic system in which the first step is the uncoupling of the receptors resulting in a decrease in the agonist-stimulated adenylate cyclase without necessarily a change in Bmax. The observed biochemical effects in rats after acute and chronic administration with clovoxamine further support the antidepressant activity of this compound.
氯伏胺是一种非三环类抗抑郁药，具有双重作用，可阻断去甲肾上腺素和5-羟色胺的再摄取。急性体外受体结合研究表明，氯伏胺对毒蕈碱、组胺能、5-羟色胺能和肾上腺素能结合位点的亲和力很小。长期给药后，氯伏胺可导致功能性β-肾上腺素能受体偶联的c-AMP反应降低。对氯伏胺（大鼠半衰期很短）和地昔帕明进行的比较表明，无论化合物是每日腹腔注射两次（10毫克/千克）还是通过渗透微型泵给药（20毫克/千克/天）持续21天，β-受体偶联的c-AMP反应的降低都是相似的。在大鼠中，通过每日两次腹腔注射或渗透微型泵长期给予氯伏胺和地昔帕明，也会导致额叶皮质中5-HT2受体数量的下调。β-受体数量（Bmax）的改变与腺苷酸环化酶活性的降低无关。这些数据支持了β-肾上腺素能系统下调的多步骤过程，其中第一步是受体解偶联，导致激动剂刺激的腺苷酸环化酶减少，而Bmax不一定改变。急性和长期给予氯伏胺后在大鼠中观察到的生化效应进一步支持了该化合物的抗抑郁活性。
