Dissociative Notes

NMDA ANTAGONISTS - Can inhibit the development of tolerance to Morphine

Memantine - Noncompetitive NMDA, HT3, NACh antagonist and D2 agonist. For use in Alzheimer's patients,

Delucemine - NMDA antagonist, SRI and has neuroprotective effects.

Alazocine - σ1 agonist, κ opioid agonist & slight NMDA antagonist

Caroverine - It acts as an N-type Ca+ blocker, competitive AMPA antagonist, and non-competitive NMDA antagonist. It also has potent antioxidant effects.

Lanicemine - Low affinity NMDA antagonist, possible anti-depressant.

Dexoxadrol - Potent PCP analogue similar to Etoxadrol. Development discontinued due to side effects such as "nightmares and hallucinations"

Etoxadrol - potent PCP analogue ^^

Hodgkinsine - alkaloid found in Psychotria colorata plants. Has antiviral, antibacterial and antifungal properties. Also μ opioid agonist & NMDA antagonist.

Psychotridine - non-competitive NMDA antagonist found in Psychotria colorata. Incredible structure!

Dexanabinol - Synthetic Cannabinoid which does not exhibit cannabinoid agonism but instead NMDA antagonism.

Dextrallophan - Morphinan, σ1 agonist & NMDA antagonist. 2x potency of DXM

Atomoxetine - Selective NRI & NMDA antagonist. Increases levels of NE & DA in prefrontal cortices by a factor of 3, however DA levels in striatum or nucleus accumbens are unaffected.

Levorphanol - μ, κ & δ agonist, 4-8x potency of M, long duration, no cross tolerance with morphine. NMDA antagonist like it's dextro counterpart.

Neramexane - Related to Memantine, NMDA antag. and NACh antag. Has antidepressant, neuroprotective and nootropic properties

Rhynchophylline - Weak NMDA antagonist found in certain Uncaria species of plant. Also present in Kratom.

Phencyclidine - PCP. NMDA antag., DRI, HT2A agonist etc.

Rolicyclidine - Sedative PCP analogue, similar to barbiturates

3-MeO-PCPy - 3-MeO version of PCPy

Tenocyclidine - Higher affinity to NMDA than PCP, deeper experience

Gacyclidine - PCP analogue with similar characteristics. Derivative of TCP.

Eticyclidine - More potent PCP analogue with similar effects.

Dieticyclidine - Low potency prodrug for eticyclidine, however it exhibits NMDA antagonistic effects in itself.

PCPr - Similar Potency to PCP

PCiPr - ^^

3-Fl 2-OH PCiPr - Similar to MXE but less potent and maybe different effects?

Dimethicyclidine - PCM with a dimethyl bond.

NEFA - Moderate affinity NMDA antagonist. PCP analogue.

3-MeO-TCP - More balanced version of TCP

3-Fluoro-TCP - Similar to the above however slightly more potent?

2-Chloro-2-Oxo-TCM - Thiopyrrole Ketamine or Tenoketamine (S-iso)

3-HO, 2-Oxo-BCPy - Opiate stimulant

PCA - blank ketamine structure minus foliage

Diphenidine - NMDA antagonist with little information.

Sabeluzole - NMDA antag. with neuroprotective and nootropic effects.

8A-PDHQ - High affinity NMDA antagonist, potency similar to MK-801.

Amantadine - Weak NMDA antagonist, NACh-a7 antagonist and MAO-A inhibitor.

Indantadol - Acts as a reversible, non-competitive MAOI and a low affinity NMDA antagonist. Nootropic potential.

Ketamine - NMDA ant. Gold Standard. Also DRI, κ & μ opioid agonist. S-Isomer 50% more potent, R-Isomer less potent, morelike alcohol

Methoxetamine - NMDA ant, DRI, SERT, μ & κ opioid agonist

2-MeO-PCP - Potent ketamine type drug. 2-MeO-PCM has effects identical to Ketamine.

3-MeO-PCP - PCP analogue with a more balanced effects profile. Smooth and relaxing.

4-MeO-PCP - Low potency PCP analogue with effects similar to low dose Ketamine.

Ketobemidone - μ opioid antagonist & NMDA antagonist. More addictive than M

3-HO-PCP - NMDA ant, DRI, μ opioid agonist (sigma?)

Remacemide - Low affinity NMDA antagonist with Sodium channel blocking properties.

MK-801 (Dizocilpine) - potent dissociative, DRI and NAch antag. Mix between PCP, Tiletamine and Rohypnol. Used to simulate psychosis in animal models.

Huperzine A - acetylcholinesterase inhibitor, NMDA antagonist

Kynurenic Acid - Product of metabolism of l-Tryptophan. Antagonist at AMPA, NMDA, Kainate glutamate and ligand for GPR35. Useful in neurological disorders

Tiletamine - NMDA antagonist similar to Ketamine and PCP but mainly used as an anaesthetic for large animals. Gets a bit nutty.

Flupirtine - Non-opioid, non-NSAID, non-steroidal painkiller. Selective neuronal potassium channel opener with NMDA antagonism.

Muscimol - Potent, selective GABAa agonist. Although non-stated, theories towards MACh and NMDA antagonism are grounded due to it's effects as a hallucinogen.

PEAQX - Competitive NMDA antagonist, 100-fold selective for GluN1/GluN2A receptors vs. GluN1/GluN2B receptors.

Midafotel - Potent, competitive NMDA antagonist, non-toxic however unsuitable for epilepse trials due to lack of neuroprotection.

AP5 - Selective competitive NMDA antagonist. Useful in isolating the actions of AMPA and kianate receptors.

AP-7 - Selective, competitive NMDA antagonist. Antagonism of NMDA causes GABA excitation to reach equilibrium in the brain. Is known to cause muscle rigidity.

LY-235,959 - Competitive NMDA antagonist. Has analgesic and neuroprotective properties as well as reducing tolerance to opioids.

2-MDP* - NMDA antagonist that produces similar effects to PCP in animals, it also has a stimulant effect 1/3 potency of Amp. Effects last around 24 hours.

Traxoprodil - NMDA antag selective for the NR2B subunit. Neuroprotective, analgesic and antidepressant. Psychoactive side effects and abuse potential at high doses.

Magnesium - Essential to the human body. Mg deficiency causes cardiovascular disease, diabetes, high blood pressure, anxiety disorders, migraines, osteoporosis and cerebral infarction. A regular amount must be taken each day.

Aptiganel - NMDA antagonist with neuroprotective properties. Side effects such as hallucinations and sedation occurs.

Budipine - Effects not well understood. NMDA antagonist and promotes the synthesis of dopamine.

Perzinfotel - Potent NMDA antagonist. HasNeuroprotective effects but lacks analgesic effects.

Orphenadrine - NMDA, MACh, H1 antagonist and NET, Na1.7, 1.8 & 1.9 and HERG Po blocker. Used against pain and muscle spasms.

Gavestinel - Selective NMDA antagonist without PCP's behavioural effects. Neuroprotective.

Ifenprodil - Selective NMDA inhibitor, specific to NR1 & NR2B subunits.

Acamprosate - Positive GABAa allosteric modulator and NMDA inhibitor. Useful in alcohol dependance and has neuroprotective properties.

Agmatine - Amino acid metabolite, binds to a2 and imidazoline receptors and blocks NMDA receptors. Has neuroprotective effects in animals with brain trauma.

Selfotel - Competitive NMDA antagonist. Has anticonvulsant, anxiolytic, analgesic and neuroprotective effects. PCP-esque effects and possible neurotoxicity.

7-Chlorokynurenic acid - NMDA antagonist with antidepressant effects

DCKA - Selective NMDA antagonist at the glycine site.

Eliprodil - NMDA antagonist without the sedative or amnesiatic effects of other NMDA antags. Does not substitute for PCP but shows neuroprotective effects.

MGluR I LIGANDS -> MGluR 1 & 5

Agonists:

Ro67-4853 - Lead compound used to investigate selective positive AM for MGluR1. Studies show that PAMs activate cAMP production, calcium mobilization and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation.

CDPPB - Selective positive AM for MGluR5. It has antipsychotic and nootropic effects and is capable of directly potentiating the depolarization of hippocampal CA1 neurons induced through NMDA administration. It also extinguishes drug-oriented memories hindering treatment and causing relapse.

Dihydroxyphenylglycine (DHGP) - Group selective (possibly) partial agonist for MGluR I. Displays cognitive enhancing effects useful in the treatment of Alzheimers and neuronal injury. Another group agonist, ACPD, can induce convulsions in neonatal rats.

Antagonists:

CPCCOEt - High selectivity but moderate affinity antagonist at MGluR1 used in research of the behavioural effects of addiction and memory. Impairs fear extinction 48hrs after conditioning but not at 2hrs implying MGluR1 is critical in long term memory.

CTEP - High potency and selectivity as an MGluR5 antagonist with high BA and long duration (18hrs). Has anti-hyperalgesic (increased sensitivity to pain) effects and has been shown to be neuroprotective and hepatoprotective (prevents damage to liver).

SIB-1893 - Selective MGluR5 antagonist and positive AM of MGluR4. Has anticonvulsant and neuroprotective effects, and reduces glutamate release.

Mavoglurant - Selective MGluR5 antagonist currently in phase 2&3 trials to treat the underlying disorder behind Fragile X Syndrome (inherited autism and retardation among male South Americans).

MTEP - Potent, selective allosteric antagonist at MGluR5. Produces neuroprotective, antidepressant, analgesic, and anxiolytic effects. Also reduces symptoms of morphine withdrawal and decreases the addictive effects of nicotine, cocaine and methamphetamine.

Fenobam - Potent, selective negative AM of mGluR5. Has anxiolytic effects comparable to benzos and also displays additional antidepressant, analgesic and anti-addictive effects.

MGluR II LIGANDS -> MGluR 2 & 3

Agonists:

Biphenylindanone A (BINA) - Potent & selective MGluR 2 positive AM. It displays anxiolytic and antipsychotic properties and decreases cocaine self administration.

LY-487,379 - Selective MGluR 2 positive AM similar to BINA.

DCG-IV - Group-selective agonist at MGluR2&3. Displays potent neuroprotective and anticonvulsant effects as well as anti-Parkinsonian effects, but also impairs the formation of memories.

Eglumegad - Group selective agonist for MGluR II with possible D2 interaction. As effective an anxiolytic as diazepam without sedation or memory impairment. Relieves the withdrawal symptoms from drugs like nicotine and morphine as well as inhibiting the development of tolerance to M. It is neuroprotective and synergistic with the neuroprotection induced by NMDA antagonists. Also reduces the effects of 5-HT2a agonists. Chronic oral admin. also markedly reduced baseline cortisol (steroid hormone released in response to stress) levels and diminished yohimbine induced stress response (fight or flight). However has low BA so the prodrug LY-544,344 is more likely to be used in trial.

LY-404,039 - Group selective agonist for MGluR II with considerable affinity for the D2 receptor. It has anxiolytic and antipsychotic effects in animal studies.

Antagonists:

PCCG-4 - Group selective antagonist for MGluR II with slight selectivity for MGluR2.

CECXG - Potent, group selective antagonist for MGluR II with reasonable selectivity for mGluR3 at 38x higher affinity than mGluR2.

LY-341,495* - Potent, group selective antagonist for MGluR II . Shows antidepressant effects while potentiating psychedelics and opioids, as well as modulating dopamine receptor function. The 1-fluorocyclopropane analog has a superior pharmacokinetic profile and similar receptor affinities, making a prodrug from this with the heptyl ester increases BA even further.

MGS-0039 - Potent, group selective antagonist for MGluR II. Produces antidepressant and anxiolytic effects, and boosts release of dopamine and serotonin in specific brain areas possibly through a similar mechanism as ketamine.

RO4491533 - Potent, group selective negative AM for MGluR II, being equipotent at mGluR2 and mGluR3. Producing antidepressant effects and reversing the effects of group II agonist LY-379,268 but at lower potency than LY-341,495.

MGluR III LIGANDS -> MGluR 4, 7 & 8

Agonists:

PHCCC - Positive allosteric modulator for MGluR4 (Receptor involved in tasting 'umami' or savory tastes), negative AM for MGluR1 (see Group I) and direct MGluR6 agonist (?).

AMN082 - Selective MGluR7 allosteric agonist. This produces and antidepressant type effect and rapid internallisation. At high doses hypo-locamotion increased significantly (shaking, flinching, general stimulated actions). Seems to also be linked to the PICK1 protein.

DCPG - MGluR8 agonist. Has anti-convulsant and neuroprotective effects and could be used to treat hyperalgesia.

L-A4P - Non selective group III MGluR agonist. Indicative of anti-parkinson effects by modulating GABAergic neurotransmission. Activation causes inhibition of GABA release in globus pallidus (involved in regulating voluntary movement) and anti-nociceptive effects.

Antagonists:

MMPIP - MGluR7 antagonist. Seems to be involved in the downstream response to cocaine in the brain.

OTHER GLUTAMATERGIC LIGANDS

WAY-213,613 - Reuptake inhibitor for subtype EAAT2, highly selective over metabotropic and ionotropic glutamate receptors. Used for research into glutamate transporters.