Mamelak M
Department of Psychiatry, Sunnybrook Medical Centre, University of Toronto, Ontario, Canada.
Neurosci Biobehav Rev. 1989 Winter;13(4):187-98. doi: 10.1016/s0149-7634(89)80053-3.
Gammahydroxybutyrate is a naturally occurring metabolite of many mammalian tissues. Although its administration produces a wide range of pharmacological effects, its normal function has never been clearly defined. GHB can induce NREM and REM sleep, anaesthesia, hypothermia, and a trance-like state which has been considered a model for petit mal epilepsy. It markedly increases brain dopamine levels. It has been touted as a central neurotransmitter or neuromodulator, and high affinity brain receptors, as well as central mechanisms for its synthesis, uptake and release have been demonstrated in support of this. But GHB is also found in many peripheral tissues and in some of these in higher concentrations than in the brain. No explanation has been offered for its presence in these tissues. A number of studies indicate that GHB can reduce energy substrate consumption in both brain and peripheral tissues, and that it can protect these tissues from the damaging effects of anoxia or excessive metabolic demand. Indeed there is some evidence to suggest that endogenous GHB levels rise under these circumstances. GHB appears to act through the endogenous opioid system, since in the brain, at least, GHB raises dynorphin levels and its metabolic and pharmacological effects can be blocked by naloxone. These, and other observations detailed in this review, suggest that GHB may function naturally in the induction and maintenance of physiological states, like sleep and hibernation, in which energy utilization is depressed. GHB may also function naturally as an endogenous protective agent when tissue energy supplies are limited.
γ-羟基丁酸是许多哺乳动物组织中天然存在的代谢产物。尽管给予γ-羟基丁酸会产生广泛的药理作用，但其正常功能从未得到明确界定。γ-羟基丁酸可诱导非快速眼动睡眠和快速眼动睡眠、麻醉、体温过低以及一种被认为是失神癫痫模型的恍惚状态。它能显著提高大脑多巴胺水平。它一直被吹捧为一种中枢神经递质或神经调节剂，并且已经证实了其具有高亲和力的脑受体以及其中枢合成、摄取和释放机制来支持这一观点。但是在许多外周组织中也发现了γ-羟基丁酸，并且在其中一些组织中的浓度高于大脑。目前尚未对其在这些组织中的存在作出解释。多项研究表明，γ-羟基丁酸可以降低大脑和外周组织中的能量底物消耗，并且它可以保护这些组织免受缺氧或代谢需求过高的损害。事实上，有一些证据表明在这些情况下内源性γ-羟基丁酸水平会升高。γ-羟基丁酸似乎是通过内源性阿片系统起作用的，因为至少在大脑中，γ-羟基丁酸会提高强啡肽水平，并且其代谢和药理作用可被纳洛酮阻断。本综述中详细阐述的这些以及其他观察结果表明，γ-羟基丁酸可能在诱导和维持能量利用降低的生理状态（如睡眠和冬眠）中发挥天然作用。当组织能量供应有限时，γ-羟基丁酸也可能作为一种内源性保护剂发挥天然作用。
