Lippman W, Pugsley T A
Can J Physiol Pharmacol. 1976 Aug;54(4):494-509. doi: 10.1139/y76-069.
The effects of viloxazine, a clinically effective antidepressant, on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake and various related pharmacological activities were determined and compared to those of the tricyclic antidepressants desimipramine, imipramine, and amitriptyline. Viloxazine inhibitied [3H]NA uptake in the mouse and rat heart, being maximally about one half as potent as imipramine with a similar onset, but shorter duration of action than imipramine. The drug did not inhibit [3H]NA uptake in rat medulla or hypothalamus in contrast to desimipramine and imipramine, but it did alter [3H]NA metabolites in a similar manner. Viloxazine, like desimipramine, was a weak blocker of mouse brain 5-HT uptake, but differed from desimipramine as it poteniated 5-HT-mediated functions in the mouse and rat, as did imipramine and amitriptyline, the latter drugs being relatively potent blockers of 5-HT uptake. Viloxazine potentiated the L-DOPA behavioural syndrome in the mouse, antagonized reserpine-induced ptosis and hypothermia in the mouse, and inhibited gastric acid secretion in the rat, but was less potent than the tricyclic antidepressants. No appreciable in vivo inhibition of monoamine oxidase (EC 1.4.3.4.) activity in the mouse was exhibited. Like imipramine, the drug potentiated the ocular effects of L-adrenaline in the rabbit. It was similar to imipramine in potency in potentiating the apomorphine-induced gnawing in the mouse. The drug antagonized oxotremorine-induced hypothermia in the mouse but differed from the tricyclic antidepressants in not exhibiting the anticholinergic effects of blocking the tremors, salivation and lacrimation. Thus, viloxazine exhibits activities related to the biogenic amines both similar to and different from the tricyclics desimipramine, imipramine, and amitriptyline. These actions appear to be of relevance with respect to the antidepressant action of this drug.
测定了临床有效的抗抑郁药维洛沙嗪对去甲肾上腺素（NA）和5-羟色胺（5-HT）摄取以及各种相关药理活性的影响，并与三环类抗抑郁药地昔帕明、丙咪嗪和阿米替林进行了比较。维洛沙嗪抑制小鼠和大鼠心脏中[3H]NA的摄取，最大效力约为丙咪嗪的一半，起效时间相似，但作用持续时间比丙咪嗪短。与地昔帕明和丙咪嗪不同，该药物不抑制大鼠延髓或下丘脑中[3H]NA的摄取，但它以类似的方式改变[3H]NA代谢物。维洛沙嗪与地昔帕明一样，是小鼠脑5-HT摄取的弱阻断剂，但与地昔帕明不同的是，它增强了小鼠和大鼠中5-HT介导的功能，丙咪嗪和阿米替林也是如此，后两种药物是5-HT摄取的相对强效阻断剂。维洛沙嗪增强了小鼠的左旋多巴行为综合征，拮抗了小鼠中利血平诱导的眼睑下垂和体温过低，并抑制了大鼠胃酸分泌，但效力低于三环类抗抑郁药。在小鼠体内未表现出对单胺氧化酶（EC 1.4.3.4.）活性的明显抑制。与丙咪嗪一样，该药物增强了兔子中L-肾上腺素的眼部效应。在增强小鼠中阿扑吗啡诱导的啃咬方面，其效力与丙咪嗪相似。该药物拮抗了小鼠中氧化震颤素诱导的体温过低，但与三环类抗抑郁药不同的是，它没有表现出阻断震颤、流涎和流泪的抗胆碱能作用。因此，维洛沙嗪表现出与生物胺相关的活性，这些活性与三环类药物地昔帕明、丙咪嗪和阿米替林既有相似之处，也有不同之处。这些作用似乎与该药物的抗抑郁作用有关。
