Obscure and Unknown: CNS 5161

*WARNING* The substances mentioned in this series have little to no record of human use, and thus the effects they have on humans are either poorly understood or entirely unknown. Much of what this information is simply hypotheses based on animal trials or very small human sample sizes. Very little information exists about their acute or long-term toxicity. Under no circumstances should any of these substances be ingested by a human outside of a clinical setting where psychological and physiological effects can be closely monitored and extremely precise doses can be prepared and TITRATED. DO NOT seek any of these out if you do not have access to those resources.


I suppose I will start a series prefaced by "New Frontiers", to ramble about potential hallucinogens that I've dug up in medical literature...
The diversity of hallucinogenic drugs can be paralleled with the diversity of animals, as in there is a bottomless boundless quantification of this diversity. There are potentially millions of undiscovered animal species. Not only that, but in the depths of the ocean there could be entire undiscovered phyla, evolutionary lineages and divergences the likes of which we cannot imagine !
Similarly, there could be entirely undiscovered classes of hallucinogenic drug. Within the boundaries of what we know, there could be psychedelics, dissociatives, and deliriants with structures vastly different from the ones we know-entirely new molecular families of substances! Perhaps this can be predicted to a degree by seeing what sorta molecules activate what sorta receptors (how do phenethylamines and tryptamines hit the same receptors???), but there is a boundless frontier to be explored! There could be entirely new classes of hallucinogens beyond the psychedelic-dissociative-deliriant trifecta, entirely new mental states that we cannot possibly comprehend. Some drugs such as glaucine, ibogaine, and muscimol seem to hint at this, being described as unique combinations of the other sorts of hallucinogens. Boundless!
I'm trying to read up on the potential dissociatives that may be arising. My search mostly consists of examining NMDA antagonists, and checking the "adverse effects" section for mentions of delusions, derealization, dissociation, numbness, etc.
*Also wow, this is as amateur as it can get, this is done with the most limited knowledge of pharmacology, neuroscience, neurology, and anything, so like, take this all with a grain of salt, I may very well just have no idea what I'm talking about and be spreading misinformation*

Without further ado, here is the first one I stumbled upon:

CNS 5161

http://chem.sis.nlm.nih.gov/chemidplus/structure/160754-76-7

CNS 5161 is a novel drug currently in the clinical trial stage for the treatment of neuropathic pain. Some dissociatives NMDA antagonists have a history of being used medically for this purpose, such as ketamine. A clinical trial1 provides the following "adverse effects": dysaesthesia, numbness, lightheadedness, derealization, drowsiness, and dizziness. These effects were described as mild. Doses were provided intravenously up to 2 mg. As stated in the conclusion however, "They do not represent a significant psychoactive effect of CNS 5161 within the dose range studied"1 However, thee described effects are reminiscent of threshold-low dose of familiar recreational dissociatives. Another paper seems to corroborate this, opening with:

"Despite encouraging effects of N-methyl-D-aspartate (NMDA) receptor antagonists in reducing neuropathic pain of different aetiologies, the clinical use of these agents has been limited by their mainly psychotropic side-effects."2
"In patients with neuropathic pain CNS 5161 is well tolerated up to a dosage of 500 µg with the most common side-effect of increasing blood pressure, mild visual disturbances and headaches."2
So what we see here is potentially an incredibly potent dissociative, highly active at ranges of 500-2000 ug. The nature of these specific psychoactive effects is unfortunately poorly described and the test subjects likely had little experience with relating or describing such effects. 

On a note of caution, 

"Prominent cardiovascular effects were seen at doses of 1 mg and above. A 15–20% increase in mean arterial pressure was apparent"1

"Some dose-dependent mortality was seen in the animal groups treated with CNS 5161, up to 25% in the highest dose group. These deaths appeared to be related to sudden respiratory failure after continuing i.v. drug infusion under anaesthesia without the assistance of mechanical ventilation."1

(anyone who can locate "Zhou D, Wang S, Hu L, et al. Neuroprotective effect of CNS 5161, a potent NMDA ion-channel antagonist, after focal cerebral ischaemia in rats. Soc for Neuroscience. 1997;23:2433. (946.2)" may be able to find out more about this...)

"Whilst the results of this study are encouraging for continued clinical development of CNS 5161, a cautious approach to the use of similar doses in patients will be necessary."1

(check this out: http://onlinelibrary.wiley.com/doi/10.1002/jlcr.1033/abstract)

Sources and further reading:

1-Walters, M. R., Bradford, A. P., Fischer, J., & Lees, K. R. (2002). Early clinical experience with the novel NMDA receptor antagonist CNS 5161. British journal of clinical pharmacology, 53(3), 305–311. 

2-Forst, T., Smith, T., Schütte, K., Marcus, P., Pfützner, A., & CNS 5161 Study Group (2007). Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain. British journal of clinical pharmacology, 64(1), 75–82
3-Zhao, Y., Robins, E., Turton, D., Brady, F., Luthra, S.K. and Årstad, E. (2006), Synthesis and characterization of N‐(2‐chloro‐5‐methylthiophenyl)‐N′‐(3‐methylthiophenyl)‐N′‐[11C]methylguanidine [11C]CNS 5161, a candidate PET tracer for functional imaging of NMDA receptors. J Label Compd Radiopharm, 49: 163-170. 

4-Zhou D, Wang S, Hu L, et al. Neuroprotective effect of CNS 5161, a potent NMDA ion-channel antagonist, after focal cerebral ischaemia in rats. Soc for Neuroscience. 1997;23:2433.