Baumann M H, Rothman R B, Ali S F
Medications Discovery Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, PO Box 5180, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Drug Alcohol Depend. 2000 May 1;59(2):143-51. doi: 10.1016/s0376-8716(99)00113-1.
Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties. Although ibogaine binds to multiple targets in the brain, recent evidence suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK-801. The purpose of the present study was to compare neurochemical and neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of rats (N=6-8/group) were decapitated 30 or 60 min after injection. Brains were harvested for analysis of dopamine (DA) and its metabolites, while trunk blood was collected for analysis of plasma corticosterone and prolactin. Ibogaine produced marked dose-dependent reductions in tissue DA with concurrent increases in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently observed in the cortex, striatum, olfactory tubercle, and hypothalamus. MK-801, on the other hand, did not reduce DA levels in any brain region but did cause modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused comparable elevations in circulating corticosterone, but only ibogaine increased prolactin. The present findings show that the effects of ibogaine on DA neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801. Thus, the wide spectrum of in vivo actions of ibogaine can probably not be explained simply on the basis of antagonism at NMDA receptors.
伊博格碱是一种从植物中提取的生物碱，具有所谓的“抗成瘾”特性。尽管伊博格碱能与大脑中的多个靶点结合，但最近的证据表明，这种药物的作用类似于MK-801，是一种N-甲基-D-天冬氨酸（NMDA）拮抗剂。本研究的目的是比较伊博格碱和MK-801在体内的神经化学和神经内分泌效应。雄性大鼠腹腔注射生理盐水、伊博格碱（10毫克/千克和100毫克/千克）或MK-801（0.1毫克/千克和1毫克/千克）。注射后30或60分钟，将大鼠断头处死（每组6 - 8只）。取出大脑用于分析多巴胺（DA）及其代谢产物，同时采集躯干血液用于分析血浆皮质酮和催乳素。伊博格碱能显著降低组织中的多巴胺水平，并同时使代谢产物3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）增加，且呈剂量依赖性。在大脑皮层、纹状体、嗅结节和下丘脑均一致观察到伊博格碱对多巴胺代谢的这种影响模式。另一方面，MK-801并没有降低任何脑区的多巴胺水平，但确实导致多巴胺代谢产物在特定脑区有适度升高。伊博格碱和MK-801能使循环中的皮质酮水平升高程度相当，但只有伊博格碱能使催乳素升高。目前的研究结果表明，MK-801不能完全模拟伊博格碱对多巴胺神经传递和神经内分泌分泌的作用。因此，伊博格碱在体内广泛的作用可能无法简单地基于其对NMDA受体的拮抗作用来解释。
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