Arylcyclohexylamines

Arylcyclohexylamines are a chemical class of pharmaceutical, designer, and experimental drugs. They are also known as arylcyclohexamines or arylcyclohexanamines.

History

Although phencyclidine (PCP) is thought to be the first arylcyclohexylamine with recognized anesthetic properties, several arylcyclohexylamines were described in the scientific literature prior to PCP, beginning with PCA (1-phenylcyclohexan-1-amine), the synthesis of which was first published in 1907. PCE was first reported in 1953, followed by PCMo (4-(1-phenyl-cyclohexyl)-morpholine[1]; see chart below for figure), which was described as a powerful sedative. Arylcyclohexylamine Parke-Davis invested heavily in anesthetic research, beginning with the 1956 synthesis of phencyclidine and later the related compound ketamine. Because of their dissociative hallucinogenic and euphoric effects, these compounds, particularly PCP and its analogues, became illicitly used recreational drugs in the 1970s. Since then, the class has grown as a result of scientific research into stimulant, analgesic, and neuroprotective agents, as well as clandestine chemists looking for new recreational drugs.

Structure

A cyclohexylamine unit is attached to an aryl moiety to form an arylcyclohexylamine. The aryl group is next to the amine. In the most basic cases, the aryl moiety is usually a phenyl ring, with some additional substitution. The amine is usually not primary; the most commonly encountered N-substituents are secondary amines such as methylamine or ethylamine, or tertiary cycloalkylamines such as piperidine and pyrrolidine.

Pharmacology

Arylcyclohexylamines have NMDA receptor antagonistic, dopamine reuptake inhibitory, and -opioid receptor agonistic properties in varying degrees. Some of these agents have also been shown to have receptor agonistic, nACh receptor antagonistic, and D2 receptor agonistic actions. Antagonism of the NMDA receptor results in anesthetic, anticonvulsant, neuroprotective, and dissociative effects; blockade of the dopamine transporter results in stimulant and euphoric effects as well as psychosis; and activation of the -opioid receptor results in analgesic and euphoric effects. Stimulation of the and D2 receptors may also help to produce hallucinogenic and psychotomimetic effects.

These are versatile agents with a wide range of potential pharmacological activities depending on the extent and scope of chemical modifications. The various substitutions that are made allow for “fine-tuning” of the resulting pharmacological profile. As an example, BTCP is a selective dopamine reuptake inhibitor[8]. PCP is primarily an NMDA antagonist, BDPC is a potent -opioid agonist, and PRE-084 is a selective sigma receptor agonist. As a result of different structural combinations, radically different pharmacology is possible.