There is a lot of very compelling research that suggests the efficacy of GABA-B antagonists as antidepressant and cognition enhancing medication. Blocking the GABA-B receptors produces several effects which are believed to contribute to the nootropic potential of antagonists at these receptors. Here is the information I was able to locate on the subject:
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GABAB receptor: a site of therapeutic benefit. https://www.ncbi.nlm...pubmed/16361115
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SGS742: the first GABA(B) receptor antagonist in clinical trials. https://www.ncbi.nlm...pubmed/15451390
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[Improvement of learning and memory functions by GABAB receptor antagonists in mice]. https://www.ncbi.nlm.../pubmed/9863249
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The GABA-B antagonist CGP 36742 prevent PTZ-kindling-provoked amnesia in rats. https://www.ncbi.nlm...pubmed/10871709
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Effects of GABAB receptor antagonists on learning and memory retention in a rat model of absence epilepsy. https://www.ncbi.nlm.../pubmed/9049596
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The GABAB receptor antagonist CGP 36,742 and the nootropic oxiracetam facilitate the formation of long-term memory. https://www.ncbi.nlm.../pubmed/8762175
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Potentiation of NMDA receptor function through somatostatin release: a possible mechanism for the cognition-enhancing activity of GABA(B) receptor antagonists. https://www.ncbi.nlm...pubmed/11522321
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Selective block of rat and human neocortex GABA(B) receptors regulating somatostatin release by a GABA(B) antagonist endowed with cognition enhancing activity. https://www.ncbi.nlm...pubmed/10587094
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Mechanism of colchicine impairment on learning and memory, and protective effect of CGP36742 in mice. https://www.ncbi.nlm.../pubmed/9098529
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GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. https://www.ncbi.nlm...pubmed/15857622
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Hippocampal levels of phosphorylated protein kinase A (phosphor-S96) are linked to spatial memory enhancement by SGS742. https://www.ncbi.nlm...pubmed/18727045
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GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. https://www.ncbi.nlm...pubmed/15857622
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Antidepressant-like activity of CGP 36742 and CGP 51176, selective GABAB receptor antagonists, in rodents. https://www.ncbi.nlm...pubmed/16921399
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Cognitive enhancement by SGS742 in OF1 mice is linked to specific hippocampal protein expression. https://www.ncbi.nlm...pubmed/19367722
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The cognitive enhancer SGS742 does not involve major known signaling cascades in OF1 mice. https://www.ncbi.nlm...pubmed/18322794
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Hippocampal synapsin isoform levels are linked to spatial memory enhancement by SGS742. https://www.ncbi.nlm...pubmed/19140176
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Novel, potent, and selective GABAC antagonists inhibit myopia development and facilitate learning and memory. https://www.ncbi.nlm...pubmed/18984654
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Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer. https://www.ncbi.nlm...pubmed/10494996
The novel mechanism of action of these drugs make them extremely interesting to me; it seems as though they would synchronize well with commonly used nootropics by boosting cognition through a separate mechanism of action than the others. I could also see combining them with an NMDA-modulator like Tianeptine to reduce any potential excitotoxicity that could be caused by the increased NMDA expression (while still allowing moderately increased NMDA expression to improve cognition). They could even have potential for a treatment to Schizophrenia because of their ability to increase NMDA expression, which chronic downregulation of has been linked to the progression of the disease. I'm not sure how well they would work for long-term use, because a lot of the studies show up-regulation of GABA-B receptors after chronic exposure; nonetheless, they seem very promising as potent and fast acting mood and cognition boosters.
I honestly cannot see why these compounds have not received more attention, they absolutely fascinate me. If anyone here has any more information on the subject or would like to discuss it in any way it would be much appreciated!