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- W2023923466 abstract "Marine organisms have yielded a variety of metabolites with neuropharmacological applications. Here we describe the isolation and pharmacological characterization of four novel, neurologically active purines 1−4, isolated from Haplosclerida sponges collected in the Republic of Palau. The structures were determined by analyses of spectral and X-ray data. Compound 1 induced convulsions upon intracerebroventricular injection into mice, with a CD50 value of 2.4 nmol/mouse. Purines 2−4 were active in mouse bioassays at higher doses. The seizurogenic activity of 1 was correlated with inhibition of neuronal GABAergic transmission, with only a modest impact on excitatory signaling, in electrophysiological recordings from hippocampal neurons. Despite having a purine template structure, the inhibitory activity of 1 was not prevented by a nonselective adenosine receptor antagonist. Thus, 1 represents a novel substituted purine that elicits convulsions through its actions on inhibitory neurotransmission. These 8-oxoisoguanine analogs comprise a new family of compounds closely related in structure to endogenous neurosignaling molecules and commonly used CNS stimulants." @default.
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- W2023923466 date "2010-08-03" @default.
- W2023923466 modified "2023-10-10" @default.
- W2023923466 title "Novel <i>N</i>-Methylated 8-Oxoisoguanines from Pacific Sponges with Diverse Neuroactivities" @default.
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- W2023923466 doi "https://doi.org/10.1021/jm100490m" @default.
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