LY341495

LY341495 is a highly potent and selective antagonist of group II metabotropic glutamate receptors with IC50 values of 21 nM and 14 nM for mGlu2 and mGlu3 receptors, respectively [1].

Glutamate is the major excitatory neurotransmitter that regulates neuronal plasticity and maintains fast synaptic transmission. The aberrant glutamate pathway has been found in a serious of neurological?problems, such as cognitive disorders, epilepsy and AD. As a selective inhibitor of group II metabotropic glutamate receptors (including mGlu2 and mGlu3), LY341495 acts as a competitive antagonist to regulate the transmission of glutamate [1 and 2].

In the functional assays, LY341495 at concentrations of 0.1 μM and 30 nM completely reversed the ACPD-induced inhibition of cAMP formation which was stimulated by forskolin in mGlu2 expressing cells and mGlu3 expressing cells, respectively. In RGT cells expressing group III mGlu receptors (mGlu4, 6, 7 and 8), LY341495 showed significant reversion of L-AP4-inhibited cAMP formation stimulated by forskolin. For mGlu4a, 7a and 8, the IC50 value of LY341495 were 22, 0.99 and 0.173 μM, respectively, which were 5 to 1000-fold higher than that for mGlu2 and mGlu3. For the group I mGlu receptors (mGlu1a and 5a), the IC50 values were 6.8 and 8.2 μM, respectively. Besides that, LY341495 was found to reversibly eliminate the long-term synaptic depression induced by DHPG in rats’ hippocampal slices [1 and 2].

In animal experiments, LY341495 was found to have effects on the post-training recognition memory. It was reported that the administration of LY341495 at different doses showed different efficacies on rats’ recognition memory. Rats treated with LY341495 at doses of 0.3, 1 and 3 mg/kg displayed a significant lower level of discrimination while LY341495 at doses of 0.05 and 0.1 mg/kg exerted a reversion of the recognition memory extinction and showed no impairment of the recognition memory [3].

References:
[1] Kingston A E, Ornstein P L, Wright R A, et al.  LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors. Neuropharmacology, 1998, 37(1): 1-12.
[2] Fitzjohn S M, Bortolotto Z A, Palmer M J, et al.  The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity. Neuropharmacology, 1998, 37(12): 1445-1458.
[3] Pitsikas N, Kaffe E, Markou A.  The metabotropic glutamate 2/3 receptor antagonist LY341495 differentially affects recognition memory in rats. Behavioural brain research, 2012, 230(2): 374-379.