5-Hydroxytryptophan-induced myoclonus in guinea pigs: mediation through 5-HT1/2 receptor subtypes.
5-Hydroxytryptophan-induced myoclonus in guinea pigs: mediation through 5-HT1/2 receptor subtypes.
复制标题
5-羟色氨酸诱导的豚鼠肌阵挛：通过 5-HT1/2 受体亚型介导。
DOI：
10.1016/s0014-2999(98)00086-7
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发表时间：
1998
影响因子：
5
通讯作者：
Carvey,PM
中科院分区：
文献类型：
--
作者：
Pappert,EJ;Goetz,CG;Stebbins,GT;Belden,M;Carvey,PM
在豚鼠中，5-羟色胺(5-羟色胺，5-羟色胺)前体和合成的5-羟色胺受体激动剂可诱发肌阵挛，但这种行为的受体亚型特异性尚未完全阐明。用卡比多巴(50 Mg)预先处理豚鼠，然后用8种5-羟色胺拮抗剂之一：N-[2-[4-(2-methoxypheny)-1-piperazinyl]-ethyl]-N-(2-pyridyl)-cyclohexancarboxamide(−)-N-叔丁基-3-[4-(2-甲氧基苯基)哌嗪-1-基]-2-苯基丙酰胺((−)-Way 100135)(5-HT1a)、甲磺酸甲硫平(5-HT1/2)、盐酸美舒尔金(5-HT2a/2C)、N[4-methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1，2，4-oxadizol-3-yl)(GR 127935)(5-HT1D)、trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-fluorophenyl)-1-基]苯酚、富马酸半酯(SR 46349)(5-HT2)、盐酸恩丹西酮(5-HT3)、和[1-[2-[methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboylate(GR 125487)(5-羟色胺)。30min后，皮下注射5-羟色氨酸(5-HTP)(75 mg/kg，sc)，由盲法观察者每隔10min测量一次肌阵挛跳跃频率，持续200min。5-羟色胺受体拮抗剂5-羟色胺受体拮抗剂甲磺酸甲硫平、GR127935和盐酸美舒尔金与安慰剂相比，对5-羟色胺诱导的肌阵挛有显著的拮抗作用，且均呈剂量依赖关系。根据三种有效拮抗剂的受体图谱，5-羟色胺诱导的肌阵挛受5-HT1/2受体系统的影响。没有任何其他受体亚型拮抗剂的显著变化表明肌阵挛与中枢5-羟色胺能机制的弥漫性激活无关。
In guinea pigs, myoclonus can be induced by 5-hydroxytryptamine (5-HT, serotonin) precursors and synthetic 5-HT receptor agonists, yet the receptor subtype specificity of this behavior is not fully delineated. Guinea pigs were pre-treated with carbidopa (50 mg) followed by one of eight 5-HT antagonists: (−)-N-tert-butyl-3-[4-(2-methoxyphenyl) piperazin-1-yl]-2-phenyl propionamide ((−)-WAY 100135) (5-HT1A), N-[2-[4-(2-methoxypheny)-1-piperazinyl]-ethyl]-N-(2-pyridyl)-cyclohexancarboxamide (WAY 100635) (5-HT1A), methiothepin mesylate (5-HT1/2), mesulergine hydrochloride (5-HT2A/2C), N[4-methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadizol-3-yl) (GR 127935) (5-HT1D), trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-fluorophenyl) propen-1-yl]phenol, hemifumarate (SR 46349) (5-HT2), ondansetron hydrochloride (5-HT3), and [1-[2-[methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboylate (GR 125487) (5-HT4). Thirty minutes later, they received 5-hydroxytryptophan (5-HTP) (75 mg/kg, sc) and myoclonic jumping rates were assessed every 10 min for 200 min by a blinded observer. Repeated measures analysis of variance of drug-induced antagonism of 5-HTP-induced myoclonus revealed a significant effect for the 5-HT receptor antagonists methiothepin mesylate, GR127935, and mesulergine hydrochloride compared to placebo, and each of these drugs inhibited 5-HTP-induced myoclonus in a dose-dependent fashion. Based on the receptor profiles of the three effective antagonists, 5-HTP-induced myoclonus is influenced by the 5-HT1/2receptor systems. The absence of a significant change with any other receptor subtype antagonist suggests that myoclonus is not related to diffuse activation of central serotonergic mechanisms.