(+)-MK 801 (Synonyms: Dizocilpine maleate;Dizocilpine hydrogen maleate;(+)-MK 801;MK 801)

Cell lines

Rat neocortical neurons

Preparation method

The solubility of this compound in DMSO is >10.45mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

10 μM, 11 sec

Applications

Cell was held at -70 mV in the whole-cell recording mode, bathed in the Mg2+-free external solution. Application of 200 μM N-Me-D-Asp elicited an inward current that rose rapidly to a peak and then decayed to a steady current. When N-Me-D-Asp and 10 μM MK-801 were applied simultaneously, the current reached nearly the same peak but was then progressively blocked with a time constant of about 11 sec. The blockade by MK-801 persisted when the cell was washed with control solution for 20 sec.

Animal models

Male Wistar rats

Dosage form

Intrathecal injection, 20 μg

Applications

The rats were given morphine (15 μg/h) for 5 days. On day 5 on which tolerance developed, at 3 h after discontinuation of morphine infusion, MK-801 was injected intrathecally 30 min before morphine challenge (15 μg). Pretreatment with MK-801 preserved its antinociceptive effect in morphine-tolerant rats in a dose-dependent manner, with amaximal effect at 60 min. The dose of 10 μg ofMK-801 resulted in only slight preservation of morphine-induced antinociception, while 5 μg of MK-801 had no effect. Injection of 20 μg of MK-801 significantly improved morphine-induced antinociception, with a maximal effect (MPE%) of up to 61%, with a 10 s tail-flick latency being defined as 100% MPE in saline-infused rats.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Huettner J E, Bean B P. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proceedings of the National Academy of Sciences, 1988, 85(4): 1307-1311.

[2] Liu C H, Cherng C H, Lin S L, et al. N-methyl-D-aspartate receptor antagonist MK-801 suppresses glial pro-inflammatory cytokine expression in morphine-tolerant rats. Pharmacology Biochemistry and Behavior, 2011, 99(3): 371-380.