Littorine is a tropane alkaloid found in a variety of plants including Datura and Atropa belladonna. It is closely related in chemical structure to atropine, hyoscyamine, and scopolamine, which all share a common biosynthetic pathway.
Afizagabar (S44819) is a first-in-class, competitive, and selective antagonist at the GABA-binding site of the α5-GABAAR, with an IC50 of 585 nM for α5β2γ2 and a Ki of 66 nM for α5β3γ2. Afizagabar enhances hippocampal synaptic plasticity and exhibits pro-cognitive efficacy[1]. Afizagabar (S44819) is a competitive α5-GABAAR antagonist (Kb=221 nM). Afizagabar selectively inhibits extrasynaptic α5-GABAARs of mouse CA1 pyramidal neurons[1]. Afizagabar (1 and 3 mg kg; i.p.) significantly diminishes the marked increase in total errors induced by Scopolamine[1]. [1]. Etherington LA, et al. Selective inhibition of extra-synaptic α5-GABAA receptors by S44819, a new therapeutic agent. Neuropharmacology. 2017;125:353-364.
Galanin is a neuropeptide with diverse biological activities. [1][2][3][4][5] It binds to rat galanin (GAL) receptor subtypes GAL1-3 (IC50s = 0.339, 1.35, and 3.31 nM, respectively) and human GAL1-3 (IC50s = 0.288, 1.62, and 12.3 nM, respectively). [1] Galanin binds to and inhibits contraction of guinea pig gastric smooth muscle cells induced by carbachol . [2] In vivo, Galanin (6 nmol, i.c.v.) increases feeding behavior in rats and increases latency to hindpaw withdrawal in response to heat and mechanical stimulation in a rat model of carrageenin-induced inflammation when administered at a dose of 2 nmol injected into the nucleus accumbens.[3][4] Galanin (5 μg, i.c.v.) also inhibits acetylcholine release induced by scopolamine in the ventral hippocampus of freely moving rats. [5]