The 1980s: d-AP5, LTP and a Decade of NMDA Receptor Discoveries

Abstract

In the 1960s and 70s, biochemical and pharmacological evidence was pointing toward glutamate as a synaptic transmitter at a number of distinct receptor classes, known as NMDA and non-NMDA receptors. The field, however, lacked a potent and highly selective antagonist to block these putative postsynaptic receptors. So, the discoveries in the early 1980s of d-AP5 as a selective NMDA receptor antagonist and of its ability to block synaptic events and plasticity were a major breakthrough leading to an explosion of knowledge about this receptor subtype. During the next 10 years, the role of NMDA receptors was established in synaptic transmission, long-term potentiation, learning and memory, epilepsy, pain, among others. Hints at pharmacological heterogeneity among NMDA receptors were followed by the cloning of separate subunits. The purpose of this review is to recognize the important contributions made in the 1980s by Graham L. Collingridge and other key scientists to the advances in our understanding of the functions of NMDA receptors throughout the central nervous system.

Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

“…The functional iGluR classes were first identified based on the selective activation or inhibition by orthosteric ligands (i.e., agonists and competitive antagonists) or channel blockers [reviewed in Mayer and Westbrook (1987b), Collingridge and Lester (1989), Lodge (2009), Dawe et al (2015), Lodge et al (2019)]. After cloning of the different iGluR subunits, it became possible to quantitatively determine the activity of these ligands at recombinant iGluR subtypes expressed in heterologous expression systems.…”

The Effectiveness of Intraoperative Ketamine and Fentanyl as Preemptive Analgesia Assessed with qNOX Score

“…Since 1980, investigations regarding the role of NMDA receptors in the pathophysiology of pain have begun to develop. 3 A subanesthetic dose of ketamine of 0.3 mg/kg, functions as analgesia with minimal effects on awareness and cognition. 2 There is sufficient clinical evidence from previous studies regarding ketamine use in the management of perioperative pain.…”

The Role of NMDAR and BDNF in Cognitive Dysfunction Induced by Different Microwave Radiation Conditions in Rats

“…These neurotransmitters jointly regulate learning and memory by transmitting various information, and changes in their levels are closely related to neurodegenerative diseases [9,10]. N-methyl-D-aspartate receptor (NMDAR) is a special excitatory amino acid receptor and a voltage-dependent ligand-gated ion channel distributed in the central nervous system, mainly in the cerebral cortex and hippocampus [11,12]. NMDARs consist of three subunits: the functional subunit NR1 and the regulatory subunits NR2 (A, B, C and D) and NR3 (A and B).…”