Bowery N G
School of Pharmacy, University of London, England.
Annu Rev Pharmacol Toxicol. 1993;33:109-47. doi: 10.1146/annurev.pa.33.040193.000545.
In conclusion, GABAB receptors appear to be of major importance in synaptic processing within the brain and are present at both post- and presynaptic sites. Their activation can hyperpolarize neurones and diminish neurotransmitter release from presynaptic terminals. We already know that drugs, i.e. baclofen, that mimic this activation are therapeutically useful, although the full significance of their use both inside and outside the brain has yet to be realized. Drugs that interfere with GABAB receptor activation should also prove to be important therapeutic agents. A number of suggestions have been proposed but it will be many years before the potential effects can be consolidated or refuted in humans. Only now are brain-penetrating GABAB antagonists being discovered, due largely to the expertise of the research group at CIBA-Geigy, Basel. The emergence of such compounds makes future studies an exciting prospect. In particular, the discovery that GABAB antagonism can suppress absence seizures in rats has provided an important therapeutic target. It is now just over ten years since we first designated the term GABAB. Since then a wealth of information has been obtained, but perhaps the best is still to come.
总之，GABAB受体似乎在大脑内的突触处理中起着至关重要的作用，且存在于突触后和突触前位点。其激活可使神经元超极化，并减少突触前终末的神经递质释放。我们已经知道，模拟这种激活的药物，即巴氯芬，具有治疗作用，尽管其在脑内和脑外使用的全部意义尚未完全明了。干扰GABAB受体激活的药物也应被证明是重要的治疗药物。已经提出了一些建议，但要在人体中证实或反驳其潜在作用还需要很多年。由于巴塞尔汽巴 - 嘉基研究小组的专业知识，目前才发现能够穿透血脑屏障的GABAB拮抗剂。这类化合物的出现使未来的研究成为一个令人兴奋的前景。特别是，发现GABAB拮抗作用可抑制大鼠失神发作，提供了一个重要的治疗靶点。自从我们首次提出GABAB这个术语至今已有十多年了。从那时起，我们已经获得了大量信息，但也许最好的还在后面。
