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Dizocilpine
Systematic (IUPAC) name
(+)-5-methyl-10,11- dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate)
Identifiers
CAS number	77086-21-6
ATC code	??
PubChem	1207
DrugBank	?
Chemical data
Formula	C16H15N
Mol. mass	221.297
Physical data
Melt. point	68.75 °C (156 °F)
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?(AU) ?(US)
Legal status
Routes	Oral, IM

Dizocilpine, also known as MK-801, is a non-competitive antagonist of the NMDA receptor. It binds inside the ion channel of the receptor and thus prevents the flow of ions such as calcium (Ca²⁺) through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug is an anti-convulsant.

The effects of MK-801 at NMDA receptors are clear and significant. NMDA receptors are key in the progression of excitotoxicity (a process in which an excessive amount of extracellular glutamate overexcites glutamate receptors and harms neurons). Thus NMDA receptor antagonists including MK-801 have been extensively studied for use in treatment of diseases with excitotoxic components, such as stroke, traumatic brain injury, and neurodegenerative diseases such as Huntington's, Alzheimer's, and amyotrophic lateral sclerosis. MK-801 has shown effectiveness in protecting neurons in cell culture and animal models of excitotoxic neurodegeneration.^[1][2][3] However, NMDA antagonists like MK-801 have largely failed to show safety and effectiveness in clinical trials, possibly due to inhibition of NMDA receptor function that is necessary for normal neuronal function. Since MK-801 is a particularly strong NMDA receptor antagonist, this drug is particularly likely to have psychotomimetic side effects (such as hallucinations) that result from NMDA receptor blockade. MK-801 had a promising future as a neuroprotective agent until neurotoxic-like effects, called Olney's Lesions, were seen in certain brain regions of test rats.^[4][5] Merck, a drug company, promptly dropped development of MK-801.

Dizocilpine may be effective as a recreational drug, and may have an active dose in the 50-100μg range. Little is known in this context about its effects, dosage, and risks. Dizocilpine's high potency makes its dosage more difficult to accurately control when compared to other similar drugs. As a result, the chances of overdosing are high. Users tend to report that the experience is not as enjoyable as other dissociative drugs, and it is often accompanied by strong auditory hallucinations. Also, dizocilpine is much longer-lasting than similar dissociative drugs such as ketamine and phencyclidine (PCP), and causes far worse amnesia and residual deficits in thinking, which have hindered its acceptance as a recreational drug.^{[citation needed]}

1. ^ Ayala GX, Tapia R. 2005. Late N-methyl-D-aspartate receptor blockade rescues hippocampal neurons from excitotoxic stress and death after 4-aminopyridine-induced epilepsy. European Journal of Neuroscience. Volume 22, Issue 12, Pages 3067-3076. Accessed January 7, 2007.
2. ^ Kocaeli H, Korfali E, Ozturk H, Kahveci N, Yilmazlar S. 2005. MK-801 improves neurological and histological outcomes after spinal cord ischemia induced by transient aortic cross-clipping in rats. Surgical Neurology. Volume 64, Supplement 2, Pages S22-S26; discussion S27. Accessed January 7, 2007.
3. ^ Mukhin AG, Ivanova SA, Knoblach SM and Faden AI. 1997. New in vitro model of traumatic neuronal injury: Evaluation of secondary injury and glutamate receptor-mediated neurotoxicity. Journal of Neurotrauma. Volume 14, Issue 9, Pages 651-663. Accessed January 7, 2007.
4. ^ Olney J, Labruyerre J and Price MT. 1989. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science, Volume 244, Issue 4910, Pages 1360-1362. Accessed January 7, 2007.
5. ^ Ellison G. 1995. The N-methyl-D-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. Brain Research. Brain Research Reviews, Volume 20, Issue 2, Pages 250-267. Accessed January 7, 2007.

• Wong et al (1986) The Anticonvulsant MK-801 is a Potent N-methyl-D-aspartate Antagonist