HT-2157

Kinase experiment:

Binding affinities for HT-2157 (SNAP 37889) and SNAP 398299 at the human Gal1, Gal2, and Gal3 receptors are determined by using the 125I-galanin displacement assay. Additionally, is tested for binding in a broad cross-reactivity panel that included G-protein-coupled receptors, ion channels, enzymes, and transporters. The ability of HT-2157 to antagonize functional responses to galanin is examined in modified HEK-293 cells (PEAKrapid cells) transiently cotransfected with the Gal3 receptor and Gαz by measuring the inhibition of adenylyl cyclase activity[1].

Animal experiment:

Rats[2] The effect of HT-2157 on locomotor activity is examined using adult male iP rats (n=12; 418-467 g). Locomotor activity is tested to ensure that any potential change in anxiety or ethanol consumption in subsequent tests is not due to any sedative property of the drug. Rats are habituated to the locomotor cells (26×26×40 cm) for 60 minute sessions which are conducted daily for three consecutive days. To minimise the effect of habituation during the treatment phase, rats are divided into two even groups which received a single injection of either HT-2157 (30 mg/kg, i.p.) or vehicle (1 ml/kg i.p.) 30 min prior to being placed in the locomotor cells for a 60 minute session. The following day the treatments are reversed so that all rats received treatment with both the vehicle and SNAP 37889 compound. Movements in terms of number of moves, move time (s) and total distance travelled (cm), are recorded automatically using TruScan 2.0 software.

References:

[1]. Swanson CJ, et al. Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17489-94.
[2]. Ash BL, et al. The galanin-3 receptor antagonist, SNAP 37889, reduces operant responding for ethanol in alcohol-preferring rats. Regul Pept. 2011 Jan 17;166(1-3):59-67.