1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances.

Beyond the well-studied dissociative drugs phencyclidine (PCP) and ketamine, hundreds of related compounds have been developed since the late 1950s, some through legitimate research and others originating from clandestine chemists. The internet in the 1990s enabled global collaboration on designing novel dissociative compounds with goals like improved duration, analgesia, and reduced toxicity. These creations, marketed as "research chemicals" or "legal highs," have entered wider distribution and sometimes reached academic labs for potential clinical applications. Two structurally distinct classes of dissociative new psychoactive substances (NPS) are the 1,2-diarylethylamines (e.g., diphenidine, fluorolintane) and β-keto-arylcyclohexylamines (e.g., methoxetamine, deschloroketamine). This chapter introduces these emerging NPS and their known pharmacology.

Study at a glance

Abstract

While phencyclidine (PCP) and ketamine remain the most well-studied and widely known dissociative drugs, a number of other agents have appeared since the late 1950s and early 1960s, when the pharmacological potential of this class was first realized. For example, hundreds of compounds have been pursued as part of legitimate research efforts to explore these agents. Some of these found their way out of the research labs and onto illicit markets of the 1960s and following decades as PCP analogs. Other "illicit analogs" apparently never appeared in the scientific literature prior to their existence on clandestine markets, thus originating as novel innovations in the minds of clandestine chemists and their colleagues. Like so much else in this world, new technologies changed this dynamic. In the 1990s individuals separated by vast geographical distances could now communicate nearly instantaneously with ease through the Internet. Some individuals used this newly found opportunity to discuss the chemistry and psychoactive effects of dissociative drugs as well as to collaborate on the design and development of novel dissociative compounds. Similar to modern pharmaceutical companies and academic researchers, these seekers tinkered with the structure of their leads pursuing goals such as improved duration of action, analgesic effects, and reduced toxicity. Whether all these goals were achieved for any individual compound remains to be seen, but their creations have been let out of the bag and are now materialized as defined compositions of matter. Moreover, these creations now exist not only in and of themselves but live on further as permutations into various novel analogs and derivatives. In some cases these compounds have made their way to academic labs where potential clinical applications have been identified. These compounds reached wider distribution when other individuals picked up on these discussions and began to market them as "research chemicals" or "legal highs". The result is a continuously evolving game that is being played between legislatures, law enforcement, and research chemical market players. Two structurally distinct classes that have appeared as dissociative-based new psychoactive substances (NPS) are the 1,2-diarylethylamines and β-keto-arylcyclohexylamines. Examples of the former include diphenidine and various analogs such as fluorolintane and N-ethyl-lanicemine, and examples of the latter are analogs of ketamine such as methoxetamine, deschloroketamine, and 2-fluoro-2-deschloroketamine. The subject of this chapter is the introduction to some of the dissociative NPS from these classes and their known pharmacology that have emerged on the market in recent years.