NMDA Receptors

The compound MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate)] is a potent anticonvulsant that is active after oral administration and whose mechanism of action is unknown. We have detected high-affinity (Kd = 37.2 +/- 2.7 nM) binding sites for [3H]MK-801 in rat brain membranes. These sites are heat-labile, stereoselective, and regionally specific, with the hippocampus showing the highest density of sites, followed by cerebral cortex, corpus striatum, and medulla-pons. There was no detectable binding in the cerebellum. MK-801 binding sites exhibited a novel pharmacological profile, since none of the major neurotransmitter candidates were active at these sites. The only compounds that were able to compete for [3H]MK-801 binding sites were substances known to block the responses of excitatory amino acids mediated by the N-methyl-D-aspartate (N-Me-D-Asp) receptor subtype. These comprised the dissociative anesthetics phencyclidine and ketamine and the sigma-type opioid N-allylnormetazocine (SKF 10,047). Neurophysiological studies in vitro, using a rat cortical-slice preparation, demonstrated a potent, selective, and noncompetitive antagonistic action of MK-801 on depolarizing responses to N-Me-D-Asp but not to kainate or quisqualate. The potencies of phencyclidine, ketamine, SKF 10,047, and the enantiomers of MK-801 as N-Me-D-Asp antagonists correlated closely (r = 0.99) with their potencies as inhibitors of [3H]MK-801 binding. This suggests that the MK-801 binding sites are associated with N-Me-D-Asp receptors and provides an explanation for the mechanism of action of MK-801 as an anticonvulsant[1].

cocaine-primed reinstatement (disruption of reconsolidation). Systemic injection of MK-801 (0.05 or 0.20 mg/kg administered intraperitoneally) in rats just prior to reactivation of the cocaine-associated memory in the CPP context attenuated subsequent cocaine-primed reinstatement, while no disruption occurred in rats that did not receive reactivation in the CPP context. However, in rats trained to self-administer cocaine, systemic administration of MK-801 just prior to either of two different types of reactivation sessions had no effect on subsequent cocaine-primed reinstatement of lever-pressing behavior. Thus, systemic administration of MK-801 disrupted the reconsolidation of a cocaine-associated memory for CPP but not for self-administration. These findings suggest that cocaine-CPP and self-administration do not use similar neurochemical processes to disrupt reconsolidation or that cocaine-associated memories in self-administering rats do not undergo reconsolidation, as assessed by lever-pressing behavior under cocaine reinstatement conditions [5].

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The effects of five administrations (3- to 4-day intervals) of morphine (MOR: 10 and 20 mg/kg, s.c.) alone, MK-801 (dizocilpine: 0.03, 0.1, 0.3 and 1 mg/kg, i.p.) alone, and combinations of MOR with MK-801 on the ambulation in mice were investigated. MK-801 at 0.3 and 1 mg/kg, but not at 0.03 and 0.1 mg/kg, significantly increased the ambulation of mice. Although the mice given repeated administrations of MK-801 (0.3 and 1 mg/kg) exhibited enhancement and reduction, respectively, in the ambulation-increasing effect of the individual doses, they showed significantly higher sensitivity than the saline-treated mice to the challenge with MOR (10 mg/kg). The repeated administrations of MOR (10 and 20 mg/kg) induced a progressive enhancement of the ambulation-increasing effect. The mice repeatedly given MOR (10 mg/kg) exhibited significant increase in the sensitivity to MK-801 (0.03-0.3 mg/kg). The coadministrations of MOR with MK-801 intensified the ambulation-increasing effect, and repeated coadministrations induced progressive enhancement of the effect, except for the combinations of MOR (10 or 20 mg/kg) with MK-801 (1 mg/kg). However, the induction of MOR sensitization was not modified by any doses of MK-801, except for the case of combination of MOR (20 mg/kg) with MK-801 (1 mg/kg) which was highly toxic (i.e., eliciting death or a moribund condition). On the other hand, simultaneous treatment with SCH 23390 (0.05 mg/kg, s.c.) or nemonapride (0.05 mg/kg, s.c.), or 4-hr pretreatment with reserpine (1 mg/kg, s.c.) strongly, and 4-hr pretreatment with alpha-methyl-p-tyrosine (200 mg/kg, i.p.) partially reduced the ambulation-increasing effect of both MOR (10 mg/kg) and MK-801 (0.3 mg/kg). Simultaneous treatment with naloxone (1 mg/kg, sc) selectively reduced the effect of MOR. However, simultaneous treatment with apomorphine (0.1 mg/kg, s.c.) did not modify the effects of either drug. These results suggest that the characteristics of the ambulation-increasing effects of MOR and MK-801 are similar to each other, and that the repeated treatments with MK-801 induce a cross-sensitization to MOR and vice versa[6].

Neurons were dissociated from the visual cortex of 2- to 6-day-old Long Evans rat pups and grown in culture for 5-43 days as described (21). Currents activated by excit-fory amino acids were measured in the whole-cell and outside-out patch-clamp configurations. Pipettes contained an internal solution (in mM) of 120 cesium methanesulfonate, 5 CsCI, 10 Cs2EGTA, 5 Mg(OH)2, 5 MgATP, 1 Na2GTP, and 10 Hepes (pH adjusted to 7.4 with CsOH). The external solution (in mM) was 160 NaCl, 2 CaC12, and 10 Hepes (pH 7.40). In whole-cell experiments, 300 nM tetrodotoxin and 10 kLM bicuculline methiodide were added to the external solution to suppress spontaneous activity. MK-801, the kind gift of Paul Anderson, was added from stock solutions of 2-50 mM in ethanol, stored at - 20'C. Final concentrations of ethanol were <0.1%. Cells or patches were bathed in control or agonist-containing external solution flowing from one of a linear array of 7-10 microcapillary tubes fed by gravity. Rapid solution changes were made by moving the array of tubes relative to the cell (whole-cell) or by moving the pipette relative to the tubes (patch). All experiments were done at 20-250C[3].

Systemic injection of Dizocilpine/MK-801 (0.05 or 0.20 mg/kg administered intraperitoneally) in rats just prior to reactivation of the cocaine-associated memory in the CPP context attenuated subsequent cocaine-primed reinstatement, while no disruption occurred in rats that did not receive reactivation in the CPP context. However, in rats trained to self-administer cocaine, systemic administration of MK-801 just prior to either of two different types of reactivation sessions had no effect on subsequent cocaine-primed reinstatement of lever-pressing behavior. Thus, systemic administration of MK-801 disrupted the reconsolidation of a cocaine-associated memory for CPP but not for self-administration. These findings suggest that cocaine-CPP and self-administration do not use similar neurochemical processes to disrupt reconsolidation or that cocaine-associated memories in self-administering rats do not undergo reconsolidation, as assessed by lever-pressing behavior under cocaine reinstatement conditions.[5]

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\n\nSubjects [5]
\nMale Sprague-Dawley and Long-Evans Hooded rats weighing 280–350 g at the start of the experiment were housed in a temperature- and humidity-controlled colony room with a 12-h light/dark cycle (lights on at 6:00 a.m.). Sprague-Dawley rats were used for all CPP studies, and our initial self-administration studies used Long-Evans rats because of their higher general activity levels and thus higher initial lever pressing during acquisition of the self-administration task. However, to ensure that there were no strain differences in the effects of Dizocilpine/MK-801 on self-administration behavior, we also used Sprague-Dawley rats to test the effects of the highest dose of MK-801 compared with Saline vehicle in this strain. No significant differences were found for the effects of MK-801, so the data from both strains were pooled. Animals undergoing self-administration were housed in a 12-h reverse light/dark cycle (lights on at 6:00 p.m.). Experiments were conducted according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and experimental protocols were approved by the University Animal Care and Use Committee. Animals were housed two per cage for the CPP studies and individually for the self-administration studies. Food and water were provided ad libitum except for when animals were engaged in experiments.\n

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\nDrug administration [5]
\n \nDizocilpine(+)-MK-801 hydrogen maleate was dissolved in sterile saline for i.p. injection (1 mL/kg). The doses chosen were 0.05 and 0.20 mg/kg, based on previous work by Przybyslawski and Sara (1997).\n

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\nSurgery [5]
\nSelf-administration surgery was conducted according to a modification of McFarland and Kalivas (2001). Rats were anesthetized with zyket (ketamine 87 mg/kg + xylazine 13 mg/kg) given intramuscularly prior to implanting a chronic indwelling i.v. catheter. The catheter was surgically implanted into the right jugular vein, and the distal end was led subcutaneously to the back between the scapulas. Catheters were constructed from Silastic tubing (9 cm; inner diameter 0.025 in, outer diameter 0.047 in) connected to a back-mount cannula pedestal, a bent 22-gauge metal cannula encased within a plastic screw connector attached to a polyester mesh (Plastics One). A small ball of silicone sealant was placed ∼2.8 cm from the end of the catheter. The right jugular vein was isolated, the most anterior portion of the vein was tied shut, and a small incision was made. The distal end of the catheter was inserted into the vein until the silicone ball was flush with the vein. The vein was secured by tying suture thread on both sides of the silicone ball; additionally, the thread on both sides was tied together. Immediately after surgery, the catheter was injected with 0.1 mL of locking solution: heparin (500 U/mL), gentamicin (5 mg/mL), and glycerol (60%) in sterile saline. Incisions were sutured, and the animal was given 5–7 d to recover. After surgery, the catheter was flushed daily with 0.1 mL of heparin (10 U/mL) and gentamicin antibiotic (5 mg/mL) in sterile saline to help protect against infection and catheter occlusion.\n

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\nBehavioral procedures [5]
\nCPP [5]
\nAll CPP studies were conducted during the same time of day. The proposed studies employed a three-compartment CPP apparatus as previously described (Brown et al. 2007). Briefly, the procedure consisted of a preconditioning preference test, training for 8 d (4 saline pairings alternating with 4 cocaine pairings), testing for CPP acquisition followed by extinction sessions, and cocaine-primed reinstatement with a 10 mg/kg, i.p. dose of cocaine (Brown et al. 2007). Except for the training days, rats had access to all three compartments of the CPP apparatus.\n

\nIn Experiment 1, we tested whether Dizocilpine/MK-801 would impair reconsolidation of the memory for the cocaine-associated context during reinstatement testing. Animals underwent preconditioning, conditioning, testing, and extinction as described above, and on Reactivation Day 1, rats received saline or MK-801 (0.05 mg/kg or 0.20 mg/kg, i.p.) 30 min prior to a cocaine injection (10 mg/kg, i.p.) and placed immediately into the central compartment of the CPP box (Reactivation Day 1). Rats were allowed to explore all three compartments. The next day, the procedure from Reactivation Day 1 was repeated (Reactivation Day 2). This procedure was given for 2 d because our previous studies using a different pharmacological agent (Brown et al. 2007) indicated that one day of memory reactivation was not sufficient to disrupt subsequent cocaine-primed reinstatement. The following day, animals were tested for cocaine-primed reinstatement without any prior injection of either saline or MK-801 before being placed into the CPP box (Reinstatement Day). Rats were allowed to explore all three compartments.\n

\nExperiment 2 was identical to Experiment 1 with the exception of the cage location where Dizocilpine/MK-801 and cocaine injection took place on Reactivation Days 1 and 2. In Experiment 2, animals were given saline or MK-801 followed by cocaine 30 min later in the home cage instead of in the CPP apparatus for the two days of “reactivation.” This was done to determine whether reactivation of the memory for the cocaine-associated context by cocaine in the CPP context was necessary for the ability of MK-801 to disrupt reconsolidation. Animals underwent preconditioning, conditioning, testing, and extinction as described above but animals were injected with saline or MK-801 (0.20 mg/kg, i.p.) 30 min prior to a cocaine injection (10 mg/kg, i.p.) in the home cage. Animals remained in the home cages, and the next day, the procedure from the first day of reactivation was repeated. The following day, animals were tested for cocaine-primed reinstatement in their CPP box without any prior microinjection of saline or MK-801, exactly as described for the Reinstatement Day in Experiment 1 above.\n

Dezocepine (MK-801) is a non-competitive NMDA receptor antagonist with high binding affinity, requiring an open pathway to block the receptor. Key pharmacokinetic characteristics include:
1. Bioavailability and Absorption
o Although specific bioavailability data for dezocepine are not available in the literature, its structural analogue, olphenadrine (an NMDA receptor antagonist with similar properties), has been shown to cross the blood-brain barrier, suggesting that dezocepine may also possess this property.
2. Metabolism and Elimination
o Studies in Reeler mice have shown that the efficacy of dezocepine is associated with GABAergic regulation, suggesting that it may be metabolized in the liver, which is involved in neurotransmitter pathways.
o Comparative pharmacokinetic data from paliperidone derivatives indicate that some drugs targeting the central nervous system may be rapidly metabolized, but the exact metabolic profile of dezocepine remains unclear.
3. Pharmacodynamic Interactions
o In the synaptic plasticity dysfunction model, dezoceppine exhibited enhanced NMDA receptor blocking, suggesting that the pharmacokinetic-pharmacodynamic relationship is context-dependent.
Further data beyond the current search results are needed for precise quantification (e.g., T_max, half-life).

Interactions…This study aimed to investigate the effects of the non-competitive NMDA glutamate receptor antagonist dezoceppine maleate (MK-801) on the neurotoxic effects of long-term high-dose dexamethasone (DEX). Results showed that DEX (120 mg/kg/day, for 7 consecutive days) impaired long-term memory and motor coordination in mice, reduced body weight, and led to death. Morphological and ultrastructural studies confirmed that long-term use of DEX alone caused hippocampal neuronal damage, particularly in the CA3 region. Damaged pyramidal neurons exhibited significant nuclear morphological changes and cytoplasmic condensation. MK-801 alone (non-toxic dose 0.3 mg/kg/day) did not alter mouse behavior or hippocampal neuronal morphology. However, it did not prevent the neurotoxic effects of DEX. Instead, it exacerbated dexamethasone (DEX)-induced neurotoxicity…In a preliminary study, a dose of 2.5 mg/kg methamphetamine (METH) instead of 1.0 mg/kg induced a delayed increase in glutamate levels in the nucleus accumbens (NAc). It is hypothesized that repeated elevations in glutamate levels induce behavioral sensitivity to the selective, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dezoczepine (MK-801), and that activation of protein kinase C (PKC) plays a crucial role in this sensitivity. This study aimed to confirm that higher doses of methamphetamine (METH) (2.5 mg/kg) induce a delayed elevation in glutamate levels and to examine the effect of the PKC inhibitor astrococcus on higher doses of METH-induced sensitivity to dezoczepine. A dose of methamphetamine (METH) of 2.5 mg/kg, rather than 1.0 mg/kg, induces a delayed elevation in glutamate levels. Acute administration of astrococcus following a single injection of METH (2.5 mg/kg) does not affect motor activity. Repeated administration of METH (2.5 mg/kg, every other day for a total of five times) induces behavioral sensitivity in mice to the motor-induced effects of the selective, non-competitive NMDA receptor antagonist dezoczepine (0.2 mg/kg). Administration of astrococcal (0.1 mg/kg) 120 minutes after each METH administration inhibited the development of behavioral sensitivity to dezocephalosine. …These results suggest that elevated glutamate levels and protein kinase C (PKC) activation are involved in delayed-induced synaptic and cellular plasticity, a potential mechanism for high-dose methamphetamine (METH)-induced behavioral sensitivity to dezocephalosine. …This study aimed to investigate the importance of sex differences in the interaction between dezocephalosine (MK-801) pretreatment and acute cold restraint stress (CRS) on pentylenetetrazole (PTZ)-induced seizures in albino Swiss mice. …This study used a CRS protocol to investigate the interaction between MK-801 pretreatment (30 minutes before CRS) and stress (followed by PTZ injection) on seizure susceptibility. Therefore, mice were divided into 6 groups: (1) PTZ control group (received PTZ only); (2) stress group (received stress and PTZ); (3) saline group (received saline and PTZ); (4) MK-801 group (received MK-801 and PTZ); (5) saline + stress group (received saline, stress and PTZ); and (6) MK-801 + stress group (received MK-801, stress and PTZ). ... Pre-administration of MK-801 (0.125, 0.25, 0.50 mg/kg) significantly enhanced the protective effect of stress against PTZ (65 mg/kg)-induced seizures and prolonged the duration of myoclonic and clonic seizures, an effect observed in both male and female mice. Compared with female mice in all groups (PTZ control, stress group, saline group, MK-801 group, saline + stress group, and MK-801 + stress group), male mice showed significantly prolonged onset times for myoclonus (males: 66.7–295.5 seconds; females: 54.0–247.5 seconds; P < 0.05) and clonic seizures (males: 123.5–789.8 seconds; females: 94.5–757.2 seconds; P < 0.05). …The findings in mice suggest that sex hormones are involved in the interaction between MK-801 pretreatment and PTZ-induced acute CRS…Adolescent male Wistar rats were exposed to ethanol vapor daily for 12 hours for 5 weeks. Eight weeks after alcohol withdrawal, the effects of intraperitoneal injection of MK-801 (0.0 to 0.1 mg/kg) on electroencephalography (EEG) and auditory event-related potentials (ERPs) were evaluated. …Adolescent alcohol exposure reduced EEG variability in the 4–6 Hz frequency band of the frontal cortex, but had no effect on EEG power or ERPs in the cortex and hippocampus. …After adolescent alcohol exposure, MK-801 significantly reduced EEG power in the parietal cortex (4–6 Hz, 6–8 Hz, 8–16 Hz, 16–32 Hz) and hippocampus (16–32 Hz), as well as EEG variability in the parietal cortex (6–8 Hz, 16–32 Hz). MK-801 significantly reduced hippocampal EEG variability (4–6 Hz, 8–16 Hz, 16–32 Hz) in control rats, but this phenomenon was not observed in the ethanol-exposed rats. Compared to the control group, MK-801 reduced the amplitude and latency of P1 event-related potentials (ERPs) in the frontal lobe of ethanol-exposed rats in response to rare tone stimuli. Conversely, MK-801 significantly reduced the amplitude and latency of P3 ERPs in the control group, but this phenomenon was not observed in the ethanol-exposed group. The conclusion is that after a prolonged withdrawal period following ethanol exposure in adolescence, the effects of MK-801 on hippocampal EEG variability and the amplitude and latency of P3 ERPs are significantly reduced. However, in adolescent rats exposed to ethanol, the inhibitory effect of MK-801 on cortical and hippocampal EEG power is enhanced. In summary, these data indicate that the NMDA receptor system undergoes persistent changes after ethanol exposure in adolescence.

[1]. 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]. Convergent Strategy to Dizocilpine MK-801 and Derivatives. J Org Chem. 2018 Apr 6;83(7):4264-4269.

[3]. 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]. MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res. 2005 Jul 19;1050(1-2):190-8.

[5]. The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats. Learn Mem. 2008 Dec 2;15(12):857-65.

[6]. Modification by MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist sensitization: evaluation by ambulation in mice. Nihon Shinkei Seishin Yakurigaku Zasshi. 1996 Feb;16(1):11-8.

[7]. Decrease of growth and differentiation factor 10 contributes to neuropathic pain through N-Me-D-Asp receptor activation. Neuroreport. 2017 May 24;28(8):444-450.

Dezocepine is a potent, non-competitive NMDA receptor (N-methyl-D-aspartate receptor) antagonist, primarily used as a research tool. This drug was once considered for the treatment of various neurodegenerative diseases or conditions in which NMDA receptors may play an important role. Due to its psychoactive effects, its application is mainly limited to animal and tissue experiments. Dezocepine can be used as an anesthetic, anticonvulsant, neuroprotective agent, nicotine receptor antagonist, and NMDA receptor antagonist. It is a maleate and also a tetracyclic antidepressant. It contains a dezocepine (1+) domain. Compound MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine maleate] is a potent anticonvulsant that acts upon oral administration, but its mechanism of action remains unclear. We detected high-affinity binding sites (Kd = 37.2 ± 2.7 nM) of [3H]MK-801 in the rat meninges. These sites exhibit thermal instability, stereoselectivity, and region specificity, with the highest density in the hippocampus, followed by the cerebral cortex, striatum, and medulla-pons. No binding was detected in the cerebellum. The MK-801 binding sites exhibit a novel pharmacological character, as none of the major neurotransmitter candidates react with these sites. The only compound that could compete with [3H]MK-801 for binding sites is a known blocker of excitatory amino acid responses mediated by the N-methyl-D-aspartate (N-Me-D-Asp) receptor subtype. These substances include the dissociative anesthetics phencyclidine and ketamine, and the sigma-type opioid N-allyl normetazocine (SKF 10,047). In vitro neurophysiological studies (using rat cortical sections) showed that MK-801 exhibits potent, selective, and non-competitive antagonism against the depolarization response of N-Me-D-Asp, but no antagonism against the depolarization response of erythrophylline or quisquiate. The potency of the enantiomers of phencyclidine, ketamine, SKF 10,047, and MK-801 as N-Me-D-Asp receptor antagonists was closely correlated with their potency as [3H]MK-801 binding inhibitors (r = 0.99). This suggests that the MK-801 binding site is associated with the N-Me-D-Asp receptor and provides an explanation for the mechanism of action of MK-801 as an anticonvulsant. [1]

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The effects of the anticonvulsant MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cycloheptene-5,10-imine maleate] on excitatory amino acid responses in cultured rat neocortical neurons were investigated using whole-cell and single-channel recording techniques. MK-801 gradually and persistently blocked N-methyl-D-aspartate (N-Me-D-Asp)-induced currents. However, during the inhibition of the N-Me-D-Asp response, there was no effect on the responses to quisquiate or ruminoidine, suggesting that the N-Me-D-Asp receptor and the ruminoidine/quisquiate receptor activate different ion channel groups. The binding and dissociation of MK-801 appear to occur only when N-Me-D-Asp-activated channels are in a neurotransmitter-activated state: MK-801 is only effective when applied concurrently with N-Me-D-Asp, and sustained exposure to N-Me-D-Asp accelerates the recovery of MK-801 blockade [time constant (τ) approximately 90 minutes at -70 to -80 mV]. Recovery of channel blockade following sustained N-Me-D-Asp application exhibits a significant voltage dependence, with faster recovery at positive potentials (τ approximately 2 minutes at +30 mV). Mg2+ is thought to block N-Me-D-Asp-activated ion channels, and at negative membrane potentials, Mg2+ inhibits the blocking effect of MK-801. In single-channel recordings with the patch-clamp facing outwards, MK-801 significantly reduced N-Me-D-Asp-induced channel activity but did not significantly alter the major single-channel conductance. Consistent with open-channel blocking mechanisms, MK-801 reduced mean channel opening time in a dose-dependent manner. [3]

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In summary, our study is the first to demonstrate that the same activation parameters and drug (MK-801) that interfere with the reconsolidation of cocaine-related memories in a conditioned position preference (CPP) task do not interfere with the reconsolidation of cocaine-related memories in a self-dosing task. Furthermore, the activation parameters of the simulated self-dosing procedure itself (which should therefore promote the effective retrieval of cocaine-related memories) also failed to make the memory susceptible to interference by MK-801. The potential to reduce persistent and unwanted memories by interfering with the reconsolidation process opens up an exciting new field for developing treatments for pathological conditions, including substance abuse. However, the complexities of memory storage and subsequent memory retrieval that could ultimately lead to memory recoding are only beginning to be elucidated, and therefore require further systematic investigation into the timing and specific parameters of reactivation. [5]

C16H15N

221.297

221.12

C, 86.84; H, 6.83; N, 6.33

70449-94-4

77086-21-6; Dizocilpine maleate;77086-22-7;(-)-Dizocilpine maleate;121917-57-5

1207

Typically exists as solid at room temperature

1.144g/cm3

320.3ºC at 760 mmHg

152.6ºC

1.632

3.479

1

1

0

17

313

0

CC12C3=CC=CC=C3CC(N1)C4=CC=CC=C24

LBOJYSIDWZQNJS-UHFFFAOYSA-N

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

1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2,4,6,10,12,14-hexaene

Neurogard; 70449-94-4; (+)-MK 801; 10,11-dihydro-5-methyl-5h-dibenzo[a,d]cyclohepten-5,10-imine; [3H]MK-801; MK-801; 5-methyl-10,11-dihydro-5H-5,10-epiminodibenzo[a,d][7]annulene; (Rac)-Dizocilpine;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)