Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
History
Phencyclidine (PCP) is believed to be the first arylcyclohexylamine with recognized anesthetic properties, but several arylcyclohexylamines were described before PCP in the scientific literature, beginning with PCA (1-phenylcyclohexan-1-amine) the synthesis of which was first published in 1907. PCE was reported in 1953 and PCMo in 1954, with the latter compound described as a potent sedative. Arylcyclohexylamines anesthetics were intensively investigated at Parke-Davis, beginning with the 1956 synthesis of phencyclidine and later the related compound ketamine. The 1970s saw the debut of these compounds, especially PCP and its analogues, as illicitly used recreational drugs due to their dissociative hallucinogenic and euphoriant effects. Since, the class has been expanded by scientific research into stimulant, analgesic, and neuroprotective agents, and also by clandestine chemists in search of novel recreational drugs.
Structure
An arylcyclohexylamine is composed of a cyclohexylamine unit with an aryl moiety attachment. The aryl group is positioned geminal to the amine. In the simplest cases, the aryl moiety is typically a phenyl ring, sometimes with additional substitution. The amine is usually not primary, secondary amines such as methylamino or ethylamino, or tertiary cycloalkylamines such as piperidino and pyrrolidino, are the most commonly encountered N-substituents.
Pharmacology
Arylcyclohexylamines varyingly possess NMDA receptor antagonistic, dopamine reuptake inhibitory, and μ-opioid receptor agonistic properties. Additionally, σ receptor agonistic, nACh receptor antagonistic, and D2 receptor agonistic actions have been reported for some of these agents. Antagonism of the NMDA receptor confers anesthetic, anticonvulsant, neuroprotective, and dissociative effects; blockade of the dopamine transporter mediates stimulant and euphoriant effects as well as psychosis in high amounts; and activation of the μ-opioid receptor causes analgesic and euphoriant effects. Stimulation of the σ and D2 receptors may also contribute to hallucinogenic and psychomimetic effects.
Versatile agents with a wide range of possible pharmacological activities depending on the extent and range to which chemical modifications are implemented. The various choice of substitutions that are made allows for "fine-tuning" of the pharmacological profile that results. As examples, BTCP is a selective dopamine reuptake inhibitor, PCP is primarily an NMDA antagonist, and BDPC is a superpotent μ-opioid agonist, while PRE-084 is a selective sigma receptor agonist. Thus, radically different pharmacology is possible through different structural combinations.
List of arylcyclohexylamines
- Other cycloalkane ring sizes have been experimented with than just purely thinking in terms of the cyclohexylamine. The requisite cycloalkylketone is reacted with PhMgBr; 3° alcohol is then reacted with NaN3; azide then reduced with LAH. Then in the final step the piperidine ring is constructed with 1-5-dibromo-pentane.
In the p- and m-fluoro pcp analog paper, pyrrolidino ring sizes were also experimented with.
Arylcyclohexylamines by Ahmadi and Kalir
Rigid
Conformationally constrained analogs have also been prepared and researched by Morieti et al.
References
External links
- From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs
- Synthesis and Effects of PCP Analogs
- Interview with a Ketamine Chemist
- PCP analogs (Cumulative)