Nature Neuroscience 8, 1139–1141 (2005); Published online 7 August 2005
Our paper identified 6-methyl-2-p-tolylaminobenzo[d]oxazin-4-one (URB754; Specs) as a monoacylglycerol lipase (MGL) inhibitor that enhances hippocampal depolarization-induced suppression of inhibition (DSI). However, in subsequent tests of non-commercial URB754, we failed to replicate these results, suggesting that a bioactive impurity was present in the commercial material. We have identified this impurity as bis(methylthio)mercurane (Supplementary Results online). Because this compound interacts with multiple targets, we tested another MGL inhibitor, methylarachidonylfluorophosphonate (MAFP), which prolonged DSI (Fig. 1), confirming that monoacylglycerol lipase contributes to the termination of DSI, as others have reported1. Another generation of endocannabinoid metabolism inhibitors is needed to test this hypothesis further.
Note: Supplementary information is available on the Nature Neuroscience website.
References
Szabo B et al. J. Physiol. (Lond.) 577, 263–280 (2006).
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The online version of the original article can be found at 10.1038/nn1521
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Makara, J., Mor, M., Fegley, D. et al. Erratum: Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus. Nat Neurosci 10, 134 (2007). https://doi.org/10.1038/nn0107-134a
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DOI: https://doi.org/10.1038/nn0107-134a
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