Arylcyclohexylamine
Encyclopedia
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer
, and experimental drug
s.
and phencyclidine
(PCP) being the first members of the class to be synthesized
. The 1970s saw the debut of these compounds, especially PCP and its analogues, as illicit drugs of abuse
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 chemist
s in search of novel recreational drugs.
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.
, dopamine reuptake inhibitor
, and μ-opioid receptor agonist
properties. Additionally, σ receptor
agonist, nACh receptor
antagonist, and D2 receptor agonist 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 psychotic 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.
| Compound >
Aryl Substituent
N Group
Cyclohexyl ring
>-
| PCA
Phenyl
NH2
| PCM Phenyl
Methylamino
| Eticyclidine
Phenyl
Ethylamino
| PCPr
Phenyl
n-Propylamino
| PCiP Phenyl
Isopropylamino
| PCBu Phenyl
n-Butylamino
| PCEOH Phenyl
Hydroxyethylamino
| PCMEA Phenyl
Methoxyethylamino
| PCEEA Phenyl
Ethoxyethylamino
| PCMPA Phenyl
Methoxypropylamino
| PCDM Phenyl
Dimethylamino
| Dieticyclidine
Phenyl
Diethylamino
| 2-HO-PCP Phenyl
Piperidine
| 2-Me-PCP Phenyl
Piperidine
| 2-MeO-PCP Phenyl
Piperidine
| 2-Keto-PCP Phenyl
Piperidine
| 2-Keto-PCE Phenyl
Ethylamino
| 4-Methyl-PCP Phenyl
Piperidine
| 4-Keto-PCP Phenyl
Piperidine
| 2'-Cl-PCP o-Chlorophenyl
Piperidine
| 2'-MeO-PCP o-Methoxyphenyl
Piperidine
| 3'-F-PCP m-Fluorophenyl
Piperidine
| 3'-Me-PCP m-Methylphenyl
Piperidine
| 3'-NH2-PCP m-Aminophenyl
Piperidine
| 3'-HO-PCP m-Hydroxyphenyl
Piperidine
| 3-MeO-PCP
m-Methoxyphenyl
Piperidine
| 3'-MeO-PCE m-Methoxyphenyl
Ethylamino
| 3'-MeO-PCPr m-Methoxyphenyl
n-Propylamino
| 3'-MeO-PCPy m-Methoxyphenyl
Pyrrolidine
| 4'-OH-PCP p-Hydroxyphenyl
Piperidine
| Methoxydine (4-MeO-PCP) p-Methoxyphenyl
Piperidine
| 4'-F-PCP p-Fluorophenyl
Piperidine
| Arketamine o-Chlorophenyl
Methylamino
| Deschloroketamine Phenyl
Methylamino
| Esketamine
o-Chlorophenyl
Methylamino
| Ethketamine o-Chlorophenyl
Ethylamino
| Ketamine
o-Chlorophenyl
Methylamino
| Methoxyketamine o-Methoxyphenyl
Methylamino
| Fluoroketamine o-Fluorophenyl
Methylamino
| Bromoketamine o-Bromophenyl
Methylamino
| Methoxetamine
m-Methoxyphenyl
Ethylamino
| Phencyclidine
(PCP) Phenyl
Piperidine
| PC3MP Phenyl
3-Methylpiperidine
| PC4MP Phenyl
4-Methylpiperidine
| Rolicyclidine
(PCPy) Phenyl
Pyrrolidine
| PCDMPy Phenyl
3,3-Dimethylpyrrolidine
| PCMo Phenyl
Morpholine
| Methoxy-PCM o-Methoxyphenyl
Morpholine
| Methyl-PCM p-Methylphenyl
Morpholine
| Hydroxy-methyl-PCM 2-Methyl-4-hydroxyphenyl
Morpholine
| TCM 2-Thienyl
Methylamino
| TCE 2-Thienyl
Ethylamino
| Tenocyclidine
(TCP) 2-Thienyl
Piperidine
| TCPy 2-Thienyl
Pyrrolidine
| Tiletamine
2-Thienyl
Ethylamino
| Gacyclidine
2-Thienyl
Piperidine
| BDPC p-Bromophenyl
Dimethylamino
| Dimetamine p-Methylphenyl
Dimethylamino
| BTCP
Benzothiophen-2-yl
Piperidine
| PRE-084
Phenyl
Morpholinylethylcarboxylate
Designer drug
Designer drug is a term used to describe drugs that are created to get around existing drug laws, usually by preparing analogs or derivatives of existing drugs by modifying their chemical structure to varying degrees, or less commonly by finding drugs with entirely different chemical structures...
, and experimental drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s.
History
The arylcyclohexylamines were originally developed as anesthetics in the 1960s with ketamineKetamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
and phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
(PCP) being the first members of the class to be synthesized
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
. The 1970s saw the debut of these compounds, especially PCP and its analogues, as illicit drugs of abuse
Drug abuse
Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...
due to their dissociative hallucinogenic and euphoriant
Euphoriant
A euphoriant is a type of psychoactive drug which tends to induce feelings of euphoria, the effects of which may include relaxation, anxiolysis, stress relief, mood lift, pleasure, and a rush although these effects are not necessary for a drug to be a euphoriant. Many euphoriants are notorious for...
effects. Since, the class has been expanded by scientific research into stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
, analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
, and neuroprotective agents, and also by clandestine chemist
Chemist
A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...
s in search of novel recreational drugs.
Chemistry
An arylcyclohexylamine is composed of a cyclohexylamineCyclohexylamine
Cyclohexylamine, also called hexahydroaniline, 1-aminocyclohexane, or aminohexahydrobenzene, is an organic chemical, an amine derived from cyclohexane. It is a clear to yellowish liquid with fishy odor, with melting point of −17.7 °C and boiling point 134.5 °C, miscible with water...
unit with an aryl
Aryl
In the context of organic molecules, aryl refers to any functional group or substituent derived from an aromatic ring, be it phenyl, naphthyl, thienyl, indolyl, etc....
moiety attachment. The aryl group is positioned geminal
Geminal
In chemistry, the term geminal refers to the relationship between two functional groups that are attached to the same atom...
to the amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
. 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
Piperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
and pyrrolidino
Pyrrolidine
Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula C4H9N. It is a cyclic secondary amine with a five-membered heterocycle containing four carbon atoms and one nitrogen atom...
, are the most commonly encountered N-substituents.
Pharmacology
Arylcyclohexylamines varyingly possess NMDA receptor antagonistNMDA receptor antagonist
NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...
, dopamine reuptake inhibitor
Dopamine reuptake inhibitor
A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...
, and μ-opioid receptor agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
properties. Additionally, σ receptor
Sigma receptor
The sigma receptors σ1 and σ2 bind to ligands such as 4-PPBP, SA 4503, ditolylguanidine, dimethyltryptamine and siramesine.- Classification :...
agonist, nACh receptor
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
antagonist, and D2 receptor agonist 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
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
mediates stimulant and euphoriant effects as well as psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
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 psychotic 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
Benocyclidine
Benocyclidine , or benzothiophenylcyclohexylpiperidine , is a psychoactive drug and research chemical of the arylcyclohexylamine and piperidine chemical classes. It acts a potent and selective dopamine reuptake inhibitor and a stimulant...
is a selective dopamine reuptake inhibitor
Dopamine reuptake inhibitor
A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...
, PCP is primarily an NMDA antagonist, and BDPC is a superpotent μ-opioid agonist, while PRE-084
PRE-084
PRE-084 is a sigma receptor agonist, selective for the σ1 subtype. It has nootropic and antidepressant actions in animal studies, as well as antitussive and reinforcing effects. PRE-084 increases the expression of GDNF....
is a selective sigma receptor
Sigma receptor
The sigma receptors σ1 and σ2 bind to ligands such as 4-PPBP, SA 4503, ditolylguanidine, dimethyltryptamine and siramesine.- Classification :...
agonist. Thus, radically different pharmacology is possible through different structural combinations.
List of arylcyclohexylamines
>-
| PCA
| PCM
| Eticyclidine
Eticyclidine
Eticyclidine is a dissociative anesthetic drug with hallucinogenic effects. It is similar in effects to phencyclidine but is slightly more potent...
| PCPr
PCPr
PCPr is a dissociative anesthetic drug with hallucinogenic and sedative effects. It is around the same potency as phencyclidine, although slightly less potent than its ethyl homologue eticyclidine, and has reportedly been sold as a designer drug in Germany and other European countries since the...
| PCiP
| PCBu
| PCEOH
| PCMEA
| PCEEA
| PCMPA
| PCDM
| Dieticyclidine
Dieticyclidine
Dieticyclidine , or diethylphenylcyclohexylamine, is a psychoactive drug and research chemical of the arylcyclohexylamine chemical class related to phencyclidine and eticyclidine . It acts as an NMDA receptor antagonist but has low potency and acts mainly as a prodrug for eticyclidine.- References :...
| 2-HO-PCP
| 2-Me-PCP
| 2-MeO-PCP
| 2-Keto-PCP
| 2-Keto-PCE
| 4-Methyl-PCP
| 4-Keto-PCP
| 2'-Cl-PCP
| 2'-MeO-PCP
| 3'-F-PCP
| 3'-Me-PCP
| 3'-NH2-PCP
| 3'-HO-PCP
| 3-MeO-PCP
3-MeO-PCP
3-Methoxyphencyclidine is a dissociative anesthetic drug with hallucinogenic and sedative effects. It is around the same potency as phencyclidine, but has slightly different effects due to its altered binding profile at various targets, particularly being somewhat more potent as an NMDA antagonist...
| 3'-MeO-PCE
| 3'-MeO-PCPr
| 3'-MeO-PCPy
| 4'-OH-PCP
| Methoxydine (4-MeO-PCP)
| 4'-F-PCP
| Arketamine
| Deschloroketamine
| Esketamine
Esketamine
Esketamine or -ketamine is a general anaesthetic of the dissociative class by way of the central nervous system and has its mode of action as an NMDA receptor antagonist...
| Ethketamine
| Ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
| Methoxyketamine
| Fluoroketamine
| Bromoketamine
| Methoxetamine
Methoxetamine
Methoxetamine or 3-MeO-2-Oxo-PCE is a chemical of the arylcyclohexylamine class which has been sold as a designer drug. It is a derivative of ketamine that also contains structural features of eticyclidine and 3-MeO-PCP...
| Phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
(PCP)
| PC3MP
| PC4MP
| Rolicyclidine
Rolicyclidine
Rolicyclidine is a dissociative anesthetic drug with hallucinogenic and sedative effects. It is similar in effects to phencyclidine but is slightly less potent and has less stimulant effects instead producing a sedative effect described as being somewhat similar to a barbiturate, but with...
(PCPy)
| PCDMPy
| PCMo
| Methoxy-PCM
| Methyl-PCM
| Hydroxy-methyl-PCM
| TCM
| TCE
| Tenocyclidine
Tenocyclidine
Tenocyclidine is a dissociative anesthetic drug with stimulant and hallucinogenic effects. It is similar in effects to phencyclidine but is considerably more potent. TCP has slightly different binding properties to PCP, with more affinity for the NMDA receptors, but less affinity for the sigma...
(TCP)
| TCPy
| Tiletamine
Tiletamine
Tiletamine is a dissociative anesthetic and pharmacologically classified as an NMDA receptor antagonist. It is related chemically and pharmacologically to other anesthetics in this family such as ketamine and phencyclidine...
| Gacyclidine
Gacyclidine
Gacyclidine is a psychoactive drug which acts as a dissociative via functioning as a non-competitive NMDA receptor antagonist. It is closely related to phencyclidine , and specifically, is a derivative of tenocyclidine .-Synthesis:...
Thiophene
Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a flat five-membered ring, it is aromatic as indicated by its extensive substitution reactions. Related to thiophene are benzothiophene and dibenzothiophene, containing the thiophene ring fused with one and two benzene...
| BDPC
| Dimetamine
| BTCP
Benocyclidine
Benocyclidine , or benzothiophenylcyclohexylpiperidine , is a psychoactive drug and research chemical of the arylcyclohexylamine and piperidine chemical classes. It acts a potent and selective dopamine reuptake inhibitor and a stimulant...
| PRE-084
PRE-084
PRE-084 is a sigma receptor agonist, selective for the σ1 subtype. It has nootropic and antidepressant actions in animal studies, as well as antitussive and reinforcing effects. PRE-084 increases the expression of GDNF....