Influence of the alpha-2 agonist oxaminozoline (S3341) on firing rate of central noradrenergic and serotonergic neurons in the rat. Comparison with clonidine.
Influence of the alpha-2 agonist oxaminozoline (S3341) on firing rate of central noradrenergic and serotonergic neurons in the rat. Comparison with clonidine.
复制标题
α-2 激动剂 oxaminozoline (S3341) 对大鼠中枢去甲肾上腺素能和血清素能神经元放电率的影响。
DOI：
10.3109/13813458609071407
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
J. Scuvée
中科院分区：
文献类型：
--
作者：
A. Dresse;J. Scuvée
记录水合氯醛麻醉的大鼠中蓝斑中央（LC）去甲肾上腺素能神经元和中缝背侧（DR）血清素能神经元的放电率。离子电渗疗法的应用或静脉注射灌注S3341（一种新型抗高血压药物）或可乐定可降低LC神经元的放电频率。根据给药方式，可乐定的效力是 S3341 的 54-63 倍。使用育亨宾和哌唑嗪证实了两种药物对 α-2 与 α-1 肾上腺素受体的选择性作用：育亨宾完全阻断 S3341 或可乐定的抑制作用，而哌唑嗪则不能阻止这种作用。 S3341 和可乐定在静脉注射期间定期降低 DR 神经元的放电率。灌注但不在离子电渗疗法应用期间。从这些实验得出的结论是，S3341和可乐定通过刺激α2自身受体对LC神经元具有直接抑制作用，并且这两种药物可能通过损害去甲肾上腺素能传递对DR神经元具有间接抑制作用。临床研究表明，S3341 引起的镇静副作用比可乐定少得多。鉴于这些药物抑制已知参与睡眠机制的单胺能神经元的放电率的效力存在巨大差异，这里报道的电生理效应可能与这些药物的镇静作用有关。
The firing rate of central locus coeruleus (LC) noradrenergic neurons and dorsal raphe (DR) serotonergic neurons was recorded in rats anaesthetized with chloral hydrate. The iontophoretic application or the i.v. perfusion of S3341, a new antihypertensive drug or clonidine decreased the frequency of discharge of LC neurons. Depending on the mode of administration clonidine was 54-63 times more potent than S3341. The selectivity of action of both drugs on alpha-2 vs. alpha-1 adrenoceptors was confirmed using yohimbine and prazosin: yohimbine completely blocked the inhibitory effect of S3341 or clonidine while prazosin did not prevent this effect. S3341 and clonidine regularly reduced the firing rate of DR neurons during i.v. perfusion but not during iontophoretic application. From these experiments is it concluded that S3341 and clonidine have a direct inhibitory effect on LC neurons via stimulation of alpha-2 autoreceptors and that both drugs have an indirect inhibitory effect on DR neurons, probably via impairment of noradrenergic transmission. Clinical studies show that S3341 induces much less sedative side effects than clonidine. In view of the great difference in the potency of these drugs to inhibit the firing rate of monoaminergic neurons which are known to be involved in sleep mechanisms, it is possible that the electrophysiological effects reported here relate to the sedative effects of these drugs.