Key Results
MRS5474 (50-500nM) was devoid of effect upon rodent excitatory synaptic
signals in hippocampal slices, except when hyperexcitability was
previously induced in vivo or ex vivo . This contrasted
with the effect of other A1R agonists. MRS5474 inhibited
GAT-1 mediated GABA uptake, an action not blocked by an
A1R antagonist but blocked by an A3R
antagonist and mimicked by an A3R agonist.
A3R was overexpressed in human hippocampal tissue
samples from patients with epilepsy that had focal resection from
surgery. MRS5474 induced a concentration-dependent potentiation of
GABA-evoked currents in oocytes micro-transplanted with human
hippocampal membranes prepared from epileptic hippocampal tissue but not
from non-epileptic tissue, an action blocked by an A3R
antagonist.