Memantine-Based Derivatives: Synthesis and Their Biological Evaluation

Alzheimer's disease (AD) is a chronic neurological disorder characterized by memory loss and cognitive decline. It is a multifactorial disease, and a number of hypotheses including glutamate hypothesis are associated with the initiation and progression of AD. The ionic glutamate receptors, mainly the N-methyl-D-aspartate receptors (NMDAR), are largely dependent on the single excitatory agonist glutamate. Glutamate is released for milliseconds at the synaptic ending to communicate with other neurons, allowing the nervous system to transmit complex motor commands and sensory information and to form thoughts and memories. Memantine is an open-channel, low-affinity, uncompetitive antagonist of NMDA receptors. It was found that the physiological receptor functions of NMDAR were unhindered by memantine and selectively block ion channels under pathological conditions, and thus maintain an optimal level of NMDA. Memantine has emerged as a promising therapeutic approach for AD. This chapter explores various methodologies for the synthesis of memantine and its pharmacological properties. The chapter also describes selective action of memantine on NMDAR and recent advancements in the field of novel drug discovery based on memantine to target NMDAR and develop an effective candidate, which may help ameliorate AD symptoms and potentially slow down the progression of disease. Understanding memantine's mechanisms of action could pave the way for novel strategies in the fight against Alzheimer's disease.