M100907, a highly selective 5-HT2A receptor antagonist and a potential atypical antipsychotic drug, facilitates induction of long-term potentiation in area CA1 of the rat hippocampal slice.

In the present study, we have shown that M100907, a highly selective 5-HT2A receptor antagonist and a putative atypical antipsychotic drug (APD), markedly potentiates N-methyl-D-aspartate (NMDA) responses and excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation of the Schaffer collaterals in CA1 hippocampal pyramidal cells. Furthermore, it enhances the induction of long-term potentiation (LTP) of CA1 synapses. If our findings can be extended to other atypical APDs, which are known to possess a relatively high affinity to 5-HT2A receptors, they may account for the purported efficacy of atypical APDs in alleviating some negative symptoms and improving cognitive and executive functions. In addition, the possibility of using M100907 as a nootropic should be further tested.