Stanford S Clare, Heal David J
Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
RenaSci Ltd, Nottingham, UK.
Brain Neurosci Adv. 2019 Jan 23;3:2398212818810682. doi: 10.1177/2398212818810682. eCollection 2019 Jan-Dec.
The late 1960s was a heyday for catecholamine research. Technological developments made it feasible to study the regulation of sympathetic neuronal transmission and to map the distribution of noradrenaline and dopamine in the brain. At last, it was possible to explain the mechanism of action of some important drugs that had been used in the clinic for more than a decade (e.g. the first generation of antidepressants) and to contemplate the rational development of new treatments (e.g. -dihydroxyphenylalanine therapy, to compensate for the dopaminergic neuropathy in Parkinson's disease, and β-adrenoceptor antagonists as antihypertensives). The fact that drug targeting noradrenergic and/or dopaminergic transmission are still the first-line treatments for many psychiatric disorders (e.g. depression, schizophrenia, and attention deficit hyperactivity disorder) is a testament to the importance of these neurotransmitters and the research that has helped us to understand the regulation of their function. This article celebrates some of the highlights of research at that time, pays tribute to some of the subsequent landmark studies, and appraises the options for where it could go next.
20世纪60年代末是儿茶酚胺研究的鼎盛时期。技术的发展使得研究交感神经传递的调节以及绘制大脑中去甲肾上腺素和多巴胺的分布成为可能。最终,人们能够解释一些已在临床上使用了十多年的重要药物(如第一代抗抑郁药)的作用机制,并设想新治疗方法的合理开发(如左旋多巴疗法,用于补偿帕金森病中的多巴胺能神经病变,以及β-肾上腺素能受体拮抗剂作为抗高血压药)。针对去甲肾上腺素能和/或多巴胺能传递的药物仍然是许多精神疾病(如抑郁症、精神分裂症和注意力缺陷多动障碍)的一线治疗方法,这一事实证明了这些神经递质的重要性以及帮助我们理解其功能调节的研究的重要性。本文回顾了当时研究的一些亮点,向随后的一些具有里程碑意义的研究致敬,并评估了未来的发展方向。