Abstract：
:Metabotropic GABAB receptors clearly modify cognitive performance in preclinical animal models, yet translation to treating human disease has been elusive. Compared to their ionotropic GABAA receptor counterpart GABAB receptors not only regulate postsynaptic excitability but also regulate diverse synaptic inputs by presynaptically inhibiting neurotransmitter release. As such, the choice of agonist, antagonist, -ve or +ve modulator as well as CNS exposure level, timing of delivery and longevity of action strongly influence the probability of unlocking the procognitive potential of GABAB receptors in human disease. Quantitative clinical analysis of target/mechanistic engagement of GABAB receptors within cognitive circuits at the level of distinct pre-synaptic and post-synaptic subpopulations is required to determine the optimal pharmacological/dosing profile for different cognitive disorders.
journal_name
Curr Opin Pharmacoljournal_title
Current opinion in pharmacologyauthors
Serrats J,Cunningham MO,Davies CHdoi
10.1016/j.coph.2017.09.012subject
Has Abstractpub_date
2017-08-01 00:00:00pages
125-132eissn
1471-4892issn
1471-4973pii
S1471-4892(17)30114-5journal_volume
35pub_type
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