Dizocilpine

Dizocilpine (MK-801), a potent anticonvulsant, is a selective and non-competitive NMDA receptor antagonist, with a Kd of 37.2 nM in rat brain membranes. Dizocilpine acts by binding to a site located within the NMDA associated ion channel and thus prevents Ca2+ flux.

Product information

CAS Number: 77086-21-6

Molecular Weight: 221.30

Formula: C16H15N

Chemical Name: (1S,9R)-9-hydrogenio-1-methyl-16-azatetracyclo[7.6.1.0²,⁷.0¹⁰,¹⁵]hexadeca-2,4,6,10,12,14-hexaene

Smiles: C[C@]12N[C@H](CC3=CC=CC=C13)C1=CC=CC=C21

InChiKey: LBOJYSIDWZQNJS-CVEARBPZSA-N

InChi: InChI=1S/C16H15N/c1-16-13-8-4-2-6-11(13)10-15(17-16)12-7-3-5-9-14(12)16/h2-9,15,17H,10H2,1H3/t15-,16+/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Dizocilpine (MK-801) progressively suppresses of current induced by NMDA. Mg2+ (10 mM) prevents Dizocilpine from blocking the N-Me-D-Asp-induced current, even when Dizocilpine is applied for a long time in the presence of NMDA. Dizocilpine blocks NMDA-activated single-channel activity in outside-out patches. Dizocilpine (MK-801; <500 μM) inhibits activation of microglia induced by LPS with increased Cox-2 protein expression in BV-2 cells. Dizocilpine (<500 μM) reduces microglial TNF-α output with an EC50 of 400 μM in BV-2 cells.

In Vivo:

Dizocilpine (MK 801) (1 mg/kg) treatment before each METH injection reduces the extent of DA depletion by 55% in striatal of mice. Dizocilpine (MK 801) (1 mg/kg) also attenuates the effects of METH on microglial activation in striatal of mice. Dizocilpine ((+)-MK 801) (0.05, 0.2 mg/kg, i.p.) attenuates subsequent cocaine-primed reinstatement without disruption in rats. Dizocilpine (MK 801) (0.2 mg/kg, i.p.) prior to two reactivation sessions in the home cage shows no suppression on subsequent cocaine-primed reinstatement. Dizocilpine (0.03, 0.1, 0.3 and 1 mg/kg, i.p.) significantly increases the ambulation of mice at 0.3 and 1 mg/kg, but not at 0.03 and 0.1 mg/kg.

References:

1. Wong EH, et al. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8.
2. Vardhan Reddy KH, et al. Convergent Strategy to Dizocilpine MK-801 and Derivatives. J Org Chem. 2018 Apr 6;83(7):4264-4269.
3. Huettner JE, et al. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1307-11.
4. Thomas DM, et al. MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res. 2005 Jul 19;1050(1-2):190-8.

Products are for research use only. Not for human use.