Arylcyclohexylamine

Last updated
Phencyclidine, the prototypical arylcyclohexylamine derivative. Phencyclidine structure.svg
Phencyclidine, the prototypical arylcyclohexylamine derivative.

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

Contents

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. PCP itself was discovered in 1926 but not researched by pharmaceutical industry until the 1950s. PCE was reported in 1953 and PCMo (4-(1-phenyl-cyclohexyl)-morpholine [1] see chart below for figure) in 1954, with PCMo described as a potent sedative. [2] Arylcyclohexylamine anesthetics were intensively investigated at Parke-Davis, beginning with the 1956 studies of PCP and later the related compound ketamine. [2] 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 that time, 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. [3] [4] [5]

Structure

General structure of arylcyclohexylamines Acha markush.png
General structure of arylcyclohexylamines

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 methylamine or ethylamine, or tertiary cycloalkylamines such as piperidine and pyrrolidine, are the most commonly encountered N-substituents.

Pharmacology

Arylcyclohexylamines varyingly possess NMDA receptor antagonistic, [6] [7] dopamine reuptake inhibitory, [8] and μ-opioid receptor agonistic [9] properties. Additionally, σ receptor agonistic, [10] nACh receptor antagonistic, [11] and D2 receptor agonistic [12] 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 psychotomimetic effects. [12]

These are versatile agents with a wide range of possible pharmacological activities depending on the extent and range to which chemical modifications are implemented. [13] [14] [15] [16] [17] [18] [19] [20] [21] 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, [8] PCP is primarily an NMDA antagonist, [6] and BDPC is a potent μ-opioid agonist, [22] while PRE-084 is a selective sigma receptor agonist. [23] Thus, radically different pharmacology is possible through different structural combinations.

Notes on numbering

PCP itself is composed of three six-membered rings, which can each be substituted by a variety of groups. These are traditionally numbered in the older research as first the cyclohexyl ring, then the phenyl, and finally the piperidine ring, with the different rings represented by prime notation (') next to the number. For instance, 4-methyl-PCP, 4'-methyl-PCP and 4''-methyl-PCP are all known compounds, with similar activity but quite different potencies.

4-Methyl-PCP, 4'-Methyl-PCP and 4''-Methyl-PCP (left to right) 4methylPCPisomer structure.png
4-Methyl-PCP, 4'-Methyl-PCP and 4''-Methyl-PCP (left to right)

However, since the widespread sale of these compounds as grey-market designer drugs, nearly all such compounds that have come to prominence either have a bare cyclohexyl ring or a 2-ketocyclohexyl ring, while the piperidine is replaced by a variety of alkyl or cycloalkyl amines and most substitution has taken place on the phenyl ring. Consequently, it is common for widely used phenyl substituted analogues such as 3'-MeO-PCP and 3'-MeO-PCE to be referred to as 3-MeO-PCP and 3-MeO-PCE without the prime, even though this is technically incorrect and could lead to confusion.

List of arylcyclohexylamines

StructuresCompoundAryl SubstituentN GroupCyclohexyl ringCAS number
PCA structure.png PCA [24] PhenylNH2-1934-71-0
PCM structure.png PCM [24] PhenylMethylamino-2201-16-3
Eticyclidine.svg Eticyclidine PhenylEthylamino-2201-15-2
PCPr structure.svg PCPr [25] Phenyln-Propylamino-18949-81-0
PCiP structure.png PCiPPhenylIsopropylamino-1195-42-2
PCAL structure.png PCAL [26] PhenylAllylamino-2185-95-7
PCBu structure.png PCBuPhenyln-Butylamino-73166-29-7
PCEOH structure.png PCEOHPhenylHydroxyethylamino-2201-22-1
PCMEA structure.png PCMEA [27] PhenylMethoxyethylamino-2201-57-2
PCEEA structure.png PCEEAPhenylEthoxyethylamino-1072895-05-6
PCMPA structure.png PCMPAPhenylMethoxypropylamino-2201-58-3
PCDM structure.png PCDM [24] PhenylDimethylamino-2201-17-4
Dieticyclidine.svg Dieticyclidine PhenylDiethylamino-2201-19-6
2-HO-PCP structure.png 2-HO-PCP [6] PhenylPiperidine2-Hydroxy94852-58-1
2-Me-PCP structure.png 2-Me-PCP [28] PhenylPiperidine2-Methyl59397-29-4
2-MeO-PCP structure.png 2-MeO-PCP [29] PhenylPiperidine2-Methoxy78636-34-7
O-PCP structure.png 2-Keto-PCPPhenylPiperidine2-Keto101688-16-8
O-PCE structure.png Eticyclidone ("O-PCE")PhenylEthylamino2-Keto6740-82-5
O-PCPr structure.png 2-Keto-PCPrPhenyln-Propylamino2-Keto
4-Me-PCP structure.png 4-Methyl-PCPPhenylPiperidine4-Methyl19420-52-1
4-Keto-PCP structure.png 4-Keto-PCP [30] PhenylPiperidine4-Keto65620-13-5
2'-Cl-PCP structure.png 2'-Cl-PCPo-ChlorophenylPiperidine-2201-31-2
3'-Cl-PCP structure.png 3'-Cl-PCP m-ChlorophenylPiperidine-2201-32-3
2'-MeO-PCP structure.png 2'-MeO-PCPo-MethoxyphenylPiperidine-2201-34-5
3'-F-PCP structure.png 3'-F-PCP [31] m-FluorophenylPiperidine-89156-99-0
3'-Me-PCP structure.png 3'-Me-PCP [32] m-TolylPiperidine-2201-30-1
3'-Me-PCPy structure.png 3'-Me-PCPy m-TolylPyrrolidine-1622348-63-3
3'-NH2-PCP structure.png 3'-NH2-PCPm-AminophenylPiperidine-72242-00-3
3-HO-PCP.png 3'-HO-PCP m-HydroxyphenylPiperidine-79787-43-2
3-MeO-PCP structure.svg 3'-MeO-PCP m-MethoxyphenylPiperidine-72242-03-6
MDPCP structure.png 3',4'-MD-PCP 3,4-MethylenedioxyphenylPiperidine-
3-MeO-PCE.svg 3'-MeO-PCE m-MethoxyphenylEthylamino-1364933-80-1
3'-OH-PCE structure.png 3'-HO-PCEm-HydroxyphenylEthylamino-
3'-MeO-PCPr structure.png 3'-MeO-PCPrm-Methoxyphenyln-Propylamino-1364933-81-2
3'-OH-PCPr structure.png 3'-HO-PCPrm-Hydroxyphenyln-Propylamino-
MDPCPr structure.png 3',4'-MD-PCPr3,4-Methylenedioxyphenyln-Propylamino-
3'-MeO-PCPy structure.png 3'-MeO-PCPy [32] m-MethoxyphenylPyrrolidine-1364933-79-8
4'-HO-PCP structure.png 4'-HO-PCPp-HydroxyphenylPiperidine-66568-88-5
4-methoxyphencyclidine.png Methoxydine (4'-MeO-PCP)p-MethoxyphenylPiperidine-2201-35-6
4'-MeO-PCE structure.png 4'-MeO-PCEp-MethoxyphenylEthylamino-
4'-F-PCP structure.png 4'-F-PCP [31] p-FluorophenylPiperidine-22904-99-0
4'-F-PCPy structure.png 4'-F-PCPyp-FluorophenylPyrrolidine-
Arketamine structure.svg Arketamine o-ChlorophenylMethylamino2-Keto33643-49-1
Deschloroketamine.png Deschloroketamine PhenylMethylamino2-Keto7063-30-1
Esketamine2DCSD.svg Esketamine o-ChlorophenylMethylamino2-Keto33643-46-8
Ketamine2DCSD.svg Ketamine o-ChlorophenylMethylamino2-Keto6740-88-1
(2R,6R)-Hydroxynorketamine Formula V1.svg Hydroxynorketamine o-ChlorophenylNH22-Keto, 6-Hydroxy81395-70-2
N-Ethylnorketamine structure.png Ethketamine o-ChlorophenylEthylamino2-Keto1354634-10-8
NPNK structure.png NPNKo-Chlorophenyln-Propylamino2-Keto2749326-65-4
Methoxyketamine.svg Methoxyketamine o-MethoxyphenylMethylamino2-Keto7063-51-6
2-MeO-NEK structure.png 2-MeO-NEK [33] o-MethoxyphenylEthylamino2-Keto
OMDCK structure.png oMDCK [34] o-TolylMethylamino2-Keto7063-37-8
MMDCK structure.png mMDCKm-TolylMethylamino2-Keto
Meta-ketamine structure.png meta-Ketaminem-ChlorophenylMethylamino2-Keto7063-53-8
Isoketamine structure.png iso-Ketamineo-ChlorophenylMethylamino4-Keto
2-Fluorodeschloroketamine.svg 2-Fluorodeschloroketamine o-FluorophenylMethylamino2-Keto111982-50-4
3FDCK structure.png 3-Fluorodeschloroketamine m-FluorophenylMethylamino2-Keto2657761-23-2
Bromoketamine structure.png Bromoketamine o-BromophenylMethylamino2-Keto120807-70-7
TFMDCK structure.png TFMDCK o-TrifluoromethylphenylMethylamino2-Keto1782149-73-8
SN35210 structure.png SN 35210 [35] o-ChlorophenylCarbomethoxybutylamino2-Keto1450615-41-4
Methoxetamine2DCSD.svg Methoxetamine m-MethoxyphenylEthylamino2-Keto1239943-76-0
Methoxmetamine.png Methoxmetamine m-MethoxyphenylMethylamino2-Keto1781829-56-8
Methoxpropamine.svg Methoxpropamine m-Methoxyphenyln-Propylamino2-Keto2504100-71-2
MXiPr structure.png MXiPr m-Methoxyphenyli-Propylamino2-Keto
Ethoxetamine structure.png Ethoxetaminem-EthoxyphenylEthylamino2-Keto
DMXE structure.svg Deoxymethoxetamine (3-Me-2'-Oxo-PCE)m-TolylEthylamino2-Keto2666932-45-0
Br-MXE structure.png Br-MXE2-bromo-5-methoxyphenylEthylamino2-Keto
HXE structure.png Hydroxetamine (HXE)m-HydroxyphenylEthylamino2-Keto1620054-73-0
HXM structure.png HXMm-HydroxyphenylMethylamino2-Keto
2F-NENDCK structure.png 2F-NENDCK o-FluorophenylEthylamino2-Keto
FXE structure.png Fluorexetamine (FXE)m-FluorophenylEthylamino2-Keto
Phencyclidine structure.svg Phencyclidine (PCP)PhenylPiperidine-77-10-1
PC3MP structure.png PC3MPPhenyl3-Methylpiperidine-2201-41-4
PC4MP structure.png PC4MPPhenyl4-Methylpiperidine-2201-42-5
Rolicyclidine.svg Rolicyclidine (PCPy)PhenylPyrrolidine-2201-39-0
PCDMPy structure.png PCDMPyPhenyl3,3-Dimethylpyrrolidine-
PCMo structure.png PCMoPhenylMorpholine-2201-40-3
2'-MeO-PCMo structure.png Methoxy-PCM [7] (2'-MeO-PCMo)o-MethoxyphenylMorpholine-1314323-88-0
3-MeO-PCMo.svg 3'-MeO-PCMo m-MethoxyphenylMorpholine-138873-80-0
4'-MeO-PCMo structure.png 4'-MeO-PCMop-MethoxyphenylMorpholine-
4'-Me-PCMo structure.png Methyl-PCM [36] (4'-Me-PCMo)p-TolylMorpholine-120803-52-3
2'-Me-4'-HO-PCMo structure.png Hydroxy-methyl-PCM2-Methyl-4-hydroxyphenylMorpholine-1314323-89-1
PYCP structure.png PYCP [37] 2-PyridinylPiperidine-
TCM structure.png TCM2-ThienylMethylamino-139401-07-3
TCE structure.png TCE2-ThienylEthylamino-101589-62-2
TCPr structure.png TCPr [38] 2-ThienylPropylamino-
Tenocyclidine.svg Tenocyclidine (TCP)2-ThienylPiperidine-21500-98-1
T3CP structure.png T3CP3-ThienylPiperidine-19420-50-9
TCPy structure.png TCPy2-ThienylPyrrolidine-22912-13-6
Tiletamine.svg Tiletamine 2-ThienylEthylamino2-Keto14176-49-9
MXTE structure.png MXTE4-Methoxy-2-thienylEthylamino2-Keto
Gacyclidine.png Gacyclidine 2-Thienyl Piperidine2-Methyl68134-81-6
Bromadol Skeletal.png BDPC p-BromophenylDimethylamino4-Phenethyl-4-hydroxy77239-98-6
C-8813.svg C-8813 p-BromophenylDimethylamino4-(thiophen-2-yl)ethyl-4-hydroxy616898-54-5
Dimetamine structure.png Dimetamine [39] p-TolylDimethylamino4-Keto65619-06-9
Ahmadi pcp 2010.svg 3''-OH-2'-Me-PCP [40] o-Tolyl3-Hydroxypiperidine-
1-(1-PhCHX)-4-Ph-4-OH-piperidine structure.png 4''-Ph-4''-OH-PCP [41] Phenyl4-Phenyl-4-hydroxypiperidine-77179-39-6
BTCP.svg BTCP [42] Benzothiophen-2-ylPiperidine-112726-66-6
BTCPy structure.png BTCPy [10] Benzothiophen-2-ylPyrrolidine-
GK-189 structure.png GK-189 [43] Naphthalen-2-ylPiperidine-81490-58-6

Other similar compounds exist where the base ring has been varied, or the amine chain replaced with other groups. [44] More cycloalkane ring sizes have been experimented with than just purely thinking in terms of the cyclohexylamine. The cyclopentyl homologue of PCP is active with around one-tenth the potency, [45] while the cycloheptyl and cyclooctyl derivatives are inactive, though some substituted arylcycloheptylamines retain activity. [46] 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. [47] Other compounds are known where the cyclohexyl base ring is replaced by rings such as norbornyl, adamantyl, [48] tetralin, oxane, thiane [49] or piperidine. [50] Conformationally constrained analogs have been prepared and researched by Morieti et al. [51]

StructureCompoundAryl SubstituentN GroupBase ringCAS number
PCPEP structure.png PCPEPPhenylPiperidineCyclopentyl23036-19-3
3F-PCHEPy structure.png 3F-PCHEPy3-FluorophenylPyrrolidineCycloheptyl
3-MeO-PBCHP structure.png 3-MeO-PBCHP3-MethoxyphenylPiperidineBicyclo[2.2.1]heptane
PADP structure.png PADP (P2AP)PhenylPiperidineAdamantyl72241-99-7
Ahmadi 2010.svg 3-MeO-PTP3-MethoxyphenylPiperidineTetralin
HHFA structure.png HHFAFused phenylAminoHexahydrofluorene
DHPQ structure.png DHPQPhenylDecahydroquinoline
POXP structure.png POXPPhenylPiperidineOxane
PTHP structure.png PTHPPhenylPiperidineThiane
MPBPip structure.png MPBPipPhenylPiperidineN-Methylpiperidine36882-04-9
BnCP structure.png BnCPBenzylPiperidineCyclohexyl22912-07-8
YNCP structure.png YNCPEthynylPiperidineCyclohexyl51165-02-7
ALCP structure.png ALCPAllylPiperidineCyclohexyl7418-80-6
Piritramide2DACS.svg Piritramide Replaced by carboxamidePiperidineN-(3-cyano-3,3-diphenylpropyl)piperidine302-41-0
PRE-084 SVG file.svg PRE-084 PhenylMorpholinylethylcarboxylateCyclohexyl138847-85-5
Clofenciclan Structural Formulae.png Clofenciclan p-ChlorophenylDiethylaminoethoxyCyclohexyl5632-52-0

Related Research Articles

<span class="mw-page-title-main">Phencyclidine</span> Dissociative hallucinogenic drug, mostly used recreationally

Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptions of sounds, and violent behavior. As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. It may also be mixed with cannabis or tobacco.

<span class="mw-page-title-main">Eticyclidine</span> Medication

Eticyclidine is a dissociative anesthetic drug with hallucinogenic effects. It is similar in effects to phencyclidine but is slightly more potent. PCE was developed by Parke-Davis in the 1970s and evaluated for anesthetic potential under the code name CI-400, but research into PCE was not continued after the development of ketamine, a similar drug with more favourable properties. Due to its similarity in effects to PCP, PCE was placed into the Schedule 1 list of illegal drugs in the 1970s, although it was only briefly abused in the 1970s and 1980s and is now little known.

<span class="mw-page-title-main">Ohmefentanyl</span> Opioid analgesic

Ohmefentanyl is an extremely potent opioid analgesic drug which selectively binds to the μ-opioid receptor.

<span class="mw-page-title-main">(+)-CPCA</span> Stimulant drug

(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine lacks the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.

<span class="mw-page-title-main">Etoxadrol</span> Chemical compound

Etoxadrol (CL-1848C) is a dissociative anaesthetic drug that has been found to be an NMDA antagonist and produce similar effects to PCP in animals. Etoxadrol, along with another related drug dexoxadrol, were developed as analgesics for use in humans, but development was discontinued in the late 1970s after patients reported side effects such as nightmares and hallucinations.

<span class="mw-page-title-main">Propiram</span> Opioid analgesic drug

Propiram is a partial μ-opioid receptor agonist and weak μ antagonist analgesic from the ampromide family of drugs related to other drugs such as phenampromide and diampromide. It was invented in 1963 in the United Kingdom by Bayer but was not widely marketed, although it saw some limited clinical use, especially in dentistry. Propiram reached Phase III clinical trials in the United States and Canada.

<span class="mw-page-title-main">Azaprocin</span> Opioid analgesic drug

Azaprocin is a drug which is an opioid analgesic with approximately ten times the potency of morphine, and a fast onset and short duration of action. It was discovered in 1963, but has never been marketed.

<span class="mw-page-title-main">Benocyclidine</span> Chemical compound

Benocyclidine, also known as benzo​thiophenyl​cyclo​hexylpiperidine (BTCP), is a psychoactive recreational drug of the arylcyclohexylamine class which is related to phencyclidine (PCP). It was first described in a patent application naming Marc Caron and colleagues at Duke University in 1997.

<span class="mw-page-title-main">3-MeO-PCP</span> Chemical compound

3-Methoxyphencyclidine (3-MeO-PCP) is a dissociative hallucinogen of the arylcyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. It has been used across Europe and the United States. In some cases, consumption has been known to be fatal. It acts mainly as an NMDA receptor antagonist, though it has also been found to interact with the sigma σ1 receptor and the serotonin transporter. The drug does not possess any opioid activity nor does it act as a dopamine reuptake inhibitor.

<span class="mw-page-title-main">4-MeO-PCP</span> Chemical compound

4-Methoxyphencyclidine is a dissociative anesthetic drug that has been sold online as a research chemical. The synthesis of 4-MeO-PCP was first reported in 1965 by the Parke-Davis medicinal chemist Victor Maddox. A 1999 review published by a chemist using the pseudonym John Q. Beagle suggested the potency of 4-MeO-PCP in man was reduced relative to PCP, two years later Beagle published a detailed description of the synthesis and qualitative effects of 4-MeO-PCP, which he said possessed 70% the potency of PCP. 4-MeO-PCP was the first arylcyclohexylamine research chemical to be sold online, it was introduced in late 2008 by a company trading under the name CBAY and was followed by several related compounds such as 3-MeO-PCP and methoxetamine. 4-MeO-PCP has lower affinity for the NMDA receptor than PCP, but higher affinity than ketamine, it is orally active in a dosage range similar to ketamine, with some users requiring doses in excess of 100 mg for desired effects. Users have reported substantial differences in active dose, these discrepancies can be partially explained by the presence of unreacted PCC and other impurities in samples sold on the grey market. 4-MeO-PCP has Ki values of 404 nM for the NMDA receptor, 713 nM for the norepinephrine transporter, 844 nM for the serotonin transporter, 296 nM for the σ1 receptor and 143 nM for the σ2 receptor.

<span class="mw-page-title-main">PCPr</span> Chemical compound

PCPr is an arylcyclohexylamine dissociative anesthetic drug with hallucinogenic and stimulant effects. It is around the same potency as phencyclidine, although slightly less potent than the ethyl homologue eticyclidine, and has reportedly been sold as a designer drug in Germany and other European countries since the late 1990s.

<span class="mw-page-title-main">G-130</span> Chemical compound

G-130 is a drug with stimulant and anorectic effects, related to phenmetrazine.

<span class="mw-page-title-main">MT-45</span> Chemical compound

MT-45 (IC-6) is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-(1,2-diphenylethyl) piperazine derivative, which is structurally unrelated to most other opioid drugs. Racemic MT-45 has around 80% the potency of morphine, with almost all opioid activity residing in the (S) enantiomer. It has been used as a lead compound from which a large family of potent opioid drugs have been developed, including full agonists, partial agonists, and antagonists at the three main opioid receptor subtypes. Fluorinated derivatives of MT-45 such as 2F-MT-45 are significantly more potent as μ-opioid receptor agonists, and one of its main metabolites 1,2-diphenylethylpiperazine also blocks NMDA receptors.

<span class="mw-page-title-main">Ephenidine</span> Dissociative anesthetic designer drug

Ephenidine is a dissociative anesthetic that has been sold online as a designer drug. It is illegal in some countries as a structural isomer of the banned opioid drug lefetamine, but has been sold in countries where it is not yet banned.

<span class="mw-page-title-main">3-MeO-PCMo</span> Chemical compound

3-MeO-PCMo is a dissociative anesthetic drug which is similar in structure to phencyclidine and been sold online as a designer drug. The inhibitory effect of 3-MeO-PCMo on the reduction in the density of the drebrin clusters by NMDAR stimulation with glutamic acid is lower than that of PCP or 3-MeO-PCP, with half maximal inhibitory concentration (IC50) values of 26.67 μM (3-MeO-PCMo), 2.02 μM (PCP) and 1.51 μM (3-MeO-PCP).

<span class="mw-page-title-main">3-HO-PCP</span> Chemical compound

3-Hydroxyphencyclidine (3-HO-PCP) is a dissociative of the arylcyclohexylamine class related to phencyclidine (PCP) that has been sold online as a designer drug.

<span class="mw-page-title-main">3-Methyl-PCPy</span> Chemical compound

3-Methyl-PCPy (3-Me-PCPy) is an arylcyclohexylamine derivative with an unusual spectrum of pharmacological effects, acting as both a potent NMDA antagonist and also a triple reuptake inhibitor which inhibits reuptake of all three monoamine neurotransmitters serotonin, dopamine and noradrenaline. It also acts as a high affinity sigma receptor ligand, selective for the σ2 subtype. It produces both stimulant and dissociative effects in animal behavioural studies.

<span class="mw-page-title-main">3-Methyl-PCP</span> Chemical compound

3-Methyl-PCP is a recreational designer drug with dissociative effects. It is an arylcyclohexylamine derivative, related to drugs such as 3'-MeO-PCP and 3'-Me-PCPy. It was first synthesised in the 1960s, but was only identified on the illicit market in Hungary in September 2020, and was made illegal in Hungary in April 2021.

<span class="mw-page-title-main">3-Fluoro-PCP</span> Chemical compound

3-Fluoro-PCP is a recreational designer drug from the arylcyclohexylamine family, with dissociative effects. It was first identified in Slovenia in October 2020, and was made illegal in Hungary in April 2021.

References

  1. ↑ "4-(1-phenyl-cyclohexyl)-morpholine". CAS Number Search - chemsrc.com. chemsrc. Retrieved 15 March 2021.
  2. 1 2 Morris H, Wallach J (2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs". Drug Testing and Analysis. 6 (7–8): 614–32. doi:10.1002/dta.1620. PMID   24678061.
  3. ↑ Valter K, Arrizabalaga P (1998). Designer Drugs Directory. Elsevier. ISBN   0-444-20525-X.
  4. ↑ Wallach J, Brandt SD (August 2018). "Phencyclidine-Based New Psychoactive Substances". New Psychoactive Substances. Handbook of Experimental Pharmacology. Vol. 252. pp. 261–303. doi:10.1007/164_2018_124. ISBN   978-3-030-10560-0. PMID   30105474.
  5. ↑ Wallach J, Brandt SD (2018). "1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances". New Psychoactive Substances. Handbook of Experimental Pharmacology. Vol. 252. pp. 305–352. doi:10.1007/164_2018_148. ISBN   978-3-030-10560-0. PMID   30196446.
  6. 1 2 3 Ahmadi A, Mahmoudi A (2005). "Synthesis and biological properties of 2-hydroxy-1-(1-phenyltetralyl)piperidine and some of its intermediates as derivatives of phencyclidine". Arzneimittel-Forschung. 55 (9): 528–32. doi:10.1055/s-0031-1296900. PMID   16229117. S2CID   29006399.
  7. 1 2 Ahmadi A, Khalili M, Hajikhani R, Naserbakht M (April 2011). "New morpholine analogues of phencyclidine: chemical synthesis and pain perception in rats". Pharmacology, Biochemistry, and Behavior. 98 (2): 227–33. doi:10.1016/j.pbb.2010.12.019. PMID   21215770. S2CID   24650035.
  8. 1 2 Chaudieu I, Vignon J, Chicheportiche M, Kamenka JM, Trouiller G, Chicheportiche R (March 1989). "Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs". Pharmacology, Biochemistry, and Behavior. 32 (3): 699–705. doi:10.1016/0091-3057(89)90020-8. PMID   2544905. S2CID   7672918.
  9. ↑ Itzhak Y, Simon EJ (August 1984). "A novel phencyclidine analog interacts selectively with mu opioid receptors". The Journal of Pharmacology and Experimental Therapeutics. 230 (2): 383–6. PMID   6086884.
  10. 1 2 He XS, Raymon LP, Mattson MV, Eldefrawi ME, de Costa BR (April 1993). "Synthesis and biological evaluation of 1-[1-(2-benzo[b]thienyl)cyclohexyl]piperidine homologues at dopamine-uptake and phencyclidine- and sigma-binding sites". Journal of Medicinal Chemistry. 36 (9): 1188–93. doi:10.1021/jm00061a009. PMID   8098066.
  11. ↑ Eterović VA, Lu R, Eakin AE, Rodríguez AD, Ferchmin PA (December 1999). "Determinants of phencyclidine potency on the nicotinic acetylcholine receptors from muscle and electric organ". Cellular and Molecular Neurobiology. 19 (6): 745–57. doi: 10.1023/A:1006905106834 . PMID   10456235. S2CID   22266452.
  12. 1 2 Seeman P, Ko F, Tallerico T (September 2005). "Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics". Molecular Psychiatry. 10 (9): 877–83. doi:10.1038/sj.mp.4001682. PMID   15852061.
  13. ↑ al-Deeb OA (May 1996). "New analgesics derived from the phencyclidine analogue thienylcyclidine". Arzneimittel-Forschung. 46 (5): 505–8. PMID   8737636.
  14. ↑ Ahmadi A, Khalili M, Hajikhani R, Hosseini H, Afshin N, Nahri-Niknafs B (March 2012). "Synthesis and study the analgesic effects of new analogues of ketamine on female wistar rats". Medicinal Chemistry. 8 (2): 246–51. doi:10.2174/157340612800493683. PMID   22385170. S2CID   42842315.
  15. ↑ Ahmadi A, Khalili M, Abbassi S, Javadi M, Mahmoudi A, Hajikhani R (2009). "Synthesis and study on analgesic effects of 1-[1-(4-methylphenyl) (cyclohexyl)] 4-piperidinol and 1-[1-(4-methoxyphenyl) (cyclohexyl)] 4-piperidinol as two new phencyclidine derivatives". Arzneimittel-Forschung. 59 (4): 202–6. doi:10.1055/s-0031-1296386. PMID   19517897. S2CID   5402425.
  16. ↑ Ahmadi A, Khalili M, Marami S, Ghadiri A, Nahri-Niknafs B (January 2014). "Synthesis and pain perception of new analogues of phencyclidine in NMRI male mice". Mini Reviews in Medicinal Chemistry. 14 (1): 64–71. doi:10.2174/1389557513666131119203551. PMID   24251803.
  17. ↑ Ahmadi A, Solati J, Hajikhani R, Pakzad S (2011). "Synthesis and analgesic effects of new pyrrole derivatives of phencyclidine in mice". Arzneimittel-Forschung. 61 (5): 296–300. doi:10.1055/s-0031-1296202. PMID   21755813. S2CID   24287727.
  18. ↑ Ahmadi A, Khalili M, Hajikhani R, Barghi L, Mihandoust F (2010). "Synthesis and determination of chronic and acute thermal and chemical pain activities of a new derivative of phencyclidine in rats". Iranian Journal of Pharmaceutical Research. 9 (4): 379–85. PMC   3870061 . PMID   24381602.
  19. ↑ Ahmadi A, Khalili M, Mihandoust F, Barghi L (2010). "Synthesis and determination of acute and chronic pain activities of 1-[1-(3-methylphenyl) (tetralyl)]piperidine as a new derivative of phencyclidine via tail immersion and formalin tests". Arzneimittel-Forschung. 60 (1): 30–5. doi:10.1055/s-0031-1296245. PMID   20184224. S2CID   23966936.
  20. ↑ Hajikhani R, Ahmadi A, Naderi N, Yaghoobi K, Shirazizand Z, Rezaee NM, Niknafs BN (2012). "Effect of phencyclidine derivatives on anxiety-like behavior using an elevated-plus maze test in mice". Advances in Clinical and Experimental Medicine. 21 (3): 307–12. PMID   23214193.
  21. ↑ Ahmadi A, Khalili M, Mirza B, Mohammadi-Diz M, Azami-Lorestani F, Ghaderi P, Nahri-Niknafs B (2017). "Synthesis and Antinociception Activities of Some Novel Derivatives of Phencyclidine with Substituted Aminobenzothiazoles". Mini Reviews in Medicinal Chemistry. 17 (1): 78–84. doi:10.2174/1389557516666160428112532. PMID   27121715.
  22. ↑ Lednicer D, VonVoigtlander PF (October 1979). "4-(p-Bromophenyl)-4-(dimethylamino)-1-phenethylcyclohexanol, an extremely potent respresentative of a new analgesic series". Journal of Medicinal Chemistry. 22 (10): 1157–8. doi:10.1021/jm00196a001. PMID   513062.
  23. ↑ Maurice T, Su TP, Parish DW, Nabeshima T, Privat A (December 1994). "PRE-084, a sigma selective PCP derivative, attenuates MK-801-induced impairment of learning in mice". Pharmacology, Biochemistry, and Behavior. 49 (4): 859–69. doi:10.1016/0091-3057(94)90235-6. PMID   7886099. S2CID   54306053.
  24. 1 2 3 Thurkauf A, de Costa B, Yamaguchi S, Mattson MV, Jacobson AE, Rice KC, Rogawski MA (May 1990). "Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues". Journal of Medicinal Chemistry. 33 (5): 1452–8. doi:10.1021/jm00167a027. PMID   2329567.
  25. ↑ Sauer C, Peters FT, Staack RF, Fritschi G, Maurer HH (April 2008). "Metabolism and toxicological detection of a new designer drug, N-(1-phenylcyclohexyl)propanamine, in rat urine using gas chromatography-mass spectrometry". Journal of Chromatography A. 1186 (1–2): 380–90. doi:10.1016/j.chroma.2007.11.002. PMID   18035363.
  26. ↑ Kalir A, Teomy S, Amir A, Fuchs P, Lee SA, Holsztynska EJ, et al. (October 1984). "N-allyl analogues of phencyclidine: chemical synthesis and pharmacological properties". Journal of Medicinal Chemistry. 27 (10): 1267–71. doi:10.1021/jm00376a006. PMID   6481761.
  27. ↑ Sauer C, Peters FT, Schwaninger AE, Meyer MR, Maurer HH (February 2009). "Investigations on the cytochrome P450 (CYP) isoenzymes involved in the metabolism of the designer drugs N-(1-phenyl cyclohexyl)-2-ethoxyethanamine and N-(1-phenylcyclohexyl)-2-methoxyethanamine". Biochemical Pharmacology. 77 (3): 444–50. doi:10.1016/j.bcp.2008.10.024. PMID   19022226.
  28. ↑ Iorio MA, Tomassini L, Mattson MV, George C, Jacobson AE (August 1991). "Synthesis, stereochemistry, and biological activity of the 1-(1-phenyl-2-methylcyclohexyl)piperidines and the 1-(1-phenyl-4-methylcyclohexyl)piperidines. Absolute configuration of the potent trans-(-)-1-(1-phenyl-2-methylcyclohexyl)piperidine". Journal of Medicinal Chemistry. 34 (8): 2615–23. doi:10.1021/jm00112a041. PMID   1875352.
  29. ↑ Ahmadi A, Mahmoudi A (2006). "Synthesis with improved yield and study on the analgesic effect of 2-methoxyphencyclidine". Arzneimittel-Forschung. 56 (5): 346–50. doi:10.1055/s-0031-1296732. PMID   16821645. S2CID   10370245.
  30. ↑ Ortiz DM, Custodio RJ, Abiero A, Botanas CJ, Sayson LV, Kim M, et al. (July 2021). "The dopaminergic alterations induced by 4-F-PCP and 4-Keto-PCP may enhance their drug-induced rewarding and reinforcing effects: Implications for abuse". Addiction Biology. 26 (4): e12981. doi:10.1111/adb.12981. PMID   33135332. S2CID   226234538.
  31. 1 2 Ogunbadeniyi AM, Adejare A (2002). "Syntheses of fluorinated phencyclidine analogs". Journal of Fluorine Chemistry. 114: 39–42. doi:10.1016/S0022-1139(01)00565-6.
  32. 1 2 Wallach J, De Paoli G, Adejare A, Brandt SD (2013). "Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogues". Drug Testing and Analysis. 6 (7–8): 633–50. doi:10.1002/dta.1468. PMID   23554350.
  33. ↑ Sayson LV, Botanas CJ, Custodio RJ, Abiero A, Kim M, Lee HJ, et al. (July 2019). "The novel methoxetamine analogs N-ethylnorketamine hydrochloride (NENK), 2-MeO-N-ethylketamine hydrochloride (2-MeO-NEK), and 4-MeO-N-ethylketamine hydrochloride (4-MeO-NEK) elicit rapid antidepressant effects via activation of AMPA and 5-HT2 receptors". Psychopharmacology. 236 (7): 2201–2210. doi:10.1007/s00213-019-05219-x. PMID   30891619. S2CID   83463722.
  34. ↑ WO 2021134086,Kruegel AC, Sames D, Hashimoto K,"Arylcyclohexylamine derivatives and their use in the treatment of psychiatric disorders",published 1 July 2021, assigned to Gilgamesh Pharmaceuticals, Inc.and The Trustees Of Columbia University In The City Of New York.
  35. ↑ Harvey M, Sleigh J, Voss L, Pruijn F, Jose J, Gamage S, Denny W (2015). "Determination of the Hypnotic Potency in Rats of the Novel Ketamine Ester Analogue SN 35210". Pharmacology. 96 (5–6): 226–32. doi:10.1159/000439598. PMID   26352278. S2CID   36017002.
  36. ↑ Ahmadi A, Khalili M, Hajikhani R, Naserbakht M (2011). "Synthesis and determination of acute and chronic pain activities of 1-[1-(4-methylphenyl) (cyclohexyl)] morpholine as a new phencyclidine derivative in rats". Arzneimittel-Forschung. 61 (2): 92–7. doi:10.1055/s-0031-1296173. PMID   21428243. S2CID   8094521.
  37. ↑ Zarantonello P, Bettini E, Paio A, Simoncelli C, Terreni S, Cardullo F (April 2011). "Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 21 (7): 2059–63. doi:10.1016/j.bmcl.2011.02.009. PMID   21334205.
  38. ↑ Wallach J, Colestock T, Cicali B, Elliott SP, Kavanagh PV, Adejare A, et al. (August 2016). "Syntheses and analytical characterizations of N-alkyl-arylcyclohexylamines" (PDF). Drug Testing and Analysis. 8 (8): 801–15. doi:10.1002/dta.1861. PMID   26360516. S2CID   1599386.
  39. ↑ Lednicer D, VonVoigtlander PF, Emmert DE (April 1980). "4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring". Journal of Medicinal Chemistry. 23 (4): 424–30. doi:10.1021/jm00178a014. PMID   7381841.
  40. ↑ Ahmadi A, Solati J, Hajikhani R, Onagh M, Javadi M (2010). "Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice". Arzneimittel-Forschung. 60 (8): 492–6. doi:10.1055/s-0031-1296317. PMID   20863005. S2CID   24803623.
  41. ↑ Itzhak Y, Kalir A, Weissman BA, Cohen S (May 1981). "New analgesic drugs derived from phencyclidine". Journal of Medicinal Chemistry. 24 (5): 496–9. doi:10.1021/jm00137a004. PMID   7241506.
  42. ↑ Vignon J, Pinet V, Cerruti C, Kamenka JM, Chicheportiche R (April 1988). "[3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP): a new phencyclidine analog selective for the dopamine uptake complex". European Journal of Pharmacology. 148 (3): 427–36. doi:10.1016/0014-2999(88)90122-7. PMID   3384005.
  43. ↑ Kamenka JM, et al. Substituted cyclic amines and pharmaceutical composition containing them. Patent US5248686, 28 September 1993
  44. ↑ Wallach JV. Structure activity relationship (SAR) studies of arylcycloalkylamines as N-methyl-D-aspartate receptor antagonists. PhD. Thesis, University of the Sciences in Philadelphia, 19 Dec 2014.
  45. ↑ Shulgin AT, Mac Lean DE (1976). "Illicit synthesis of phencyclidine (PCP) and several of its analogs". Clinical Toxicology. 9 (4): 553–60. doi:10.3109/15563657608988157. PMID   975751.
  46. ↑ Sun S, Wallach J, Adejare A (2014). "Syntheses and N-methyl-D-aspartate receptor antagonist pharmacology of fluorinated arylcycloheptylamines". Medicinal Chemistry. 10 (8). Shariqah (United Arab Emirates): 843–52. doi:10.2174/1573406410666140428104444. PMID   24773376.
  47. ↑ McQuinn RL, Cone EJ, Shannon HE, Su TP (December 1981). "Structure-activity relationships of the cycloalkyl ring of phencyclidine". Journal of Medicinal Chemistry. 24 (12): 1429–32. doi:10.1021/jm00144a011. PMID   7310819.
  48. ↑ Eaton TA, Houk KN, Watkins SF, Fronczek FR (April 1983). "Geometries and conformational processes in phencyclidine and a rigid adamantyl analogue: variable-temperature NMR, X-ray crystallographic, and molecular mechanics studies". Journal of Medicinal Chemistry. 26 (4): 479–86. doi:10.1021/jm00358a005. PMID   6834381.
  49. ↑ Sisco E, Urbas A. Identification and Characterization of Designer Phencyclidines (PCPs) in Forensic Casework
  50. ↑ Gerhard O, Eberhard E. 4-amino-piperidines. US3311624A
  51. ↑ Moriarty RM, Enache LA, Zhao L, Gilardi R, Mattson MV, Prakash O (February 1998). "Rigid phencyclidine analogues. Binding to the phencyclidine and sigma 1 receptors". Journal of Medicinal Chemistry. 41 (4): 468–77. doi:10.1021/jm970059p. PMID   9484497.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.