Review of Synthetic Approaches to Dizocilpine

N-Methyl-D-aspartate (NMDA) receptors, together with AMPA and kainite receptors, belong to the family of ionotropic glutamate receptors. NMDA receptors play a crucial role in neuronal plasticity and cognitive functions. Overactivation of those receptors leads to glutamate-induced excitotoxicity, which could be suppressed by NMDA antagonists. Dizocilpine was firstly reported in 1982 as an NMDA receptor antagonist with anticonvulsive properties, but due to serious side effects like neuronal vacuolization, its use in human medicine is restricted. However, dizocilpine is still used as a validated tool to induce the symptoms of schizophrenia in animal models and also as a standard for comparative purposes to newly developed NMDA receptor antagonists. For this reason, the synthesis of dizocilpine and especially its more active enantiomer (+)-dizocilpine is still relevant. In this review, we bring a collection of various synthetic approaches leading to dizocilpine and its analogues.

Automated summary

NMDA receptors are crucial for neuronal plasticity and cognitive functions, but overactivation can lead to excitotoxicity. Dizocilpine, an NMDA receptor antagonist with anticonvulsive properties, is restricted for use in human medicine due to serious side effects, but still used in animal models.