Overview
- Traynelis, S.F. et al. (2010) Pharmacol. Rev. 62, 405.
Alomone Labs (+)-MK 801 maleate inhibits NMDA (NR1+NR2A) channels expressed in Xenopus oocytes.A. Time course of NMDA currents elicited with 100 µM glutamate and 100 µM glycine, every 50 sec, while membrane potential was held at -80 mV. 0.1 and 1 µM (+)-MK 801 maleate (#M-230) applied for 3 min each (as indicated) inhibited current amplitude. B. Superimposed current traces taken from the experiment described in A.
MK-801 maleate is a non competitive, high affinity, open channel blocker of the N-methyl-D-aspartate (NMDA) receptors. MK-801 blocks NMDA-induced currents in a voltage-dependent manner, preventing the influx of calcium ions through the channel. This compound is being used as a pharmacological tool to explore NMDA receptor function.
The drug exists in two isomers (+) and (-) and displays several biological properties such as anticonvulsant and anesthetic. MK-801 is not used clinically because it has been shown to promote the development of brain lesions in rats1,2.
NMDA receptors are ion channels gated by the major excitatory neurotransmitter in the mammalian central nervous system, glutamate. Glutamate-mediated signaling is important for basic neuron-to-neuron signaling and neuronal processes such as learning, memory and pain perception3.
In rats, MK-801 has the ability to induce a characteristic behavioral syndrome with ataxia, stereotypic behavior and hyperlocomotion. In addition, the compound can induce necrosis in a small population of neurons in the cortex of rats4.
It has also been discerned that MK-801 induces schizophrenia-like symptoms in rodents, including cognitive functions5.
