3-Hydroxyphencyclidine (3-HO-PCP) is a

dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

of the

arylcyclohexylamine 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 recog ...

class related to

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted percept ...

(PCP) that has been sold online as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. D ...

Pharmacology

3-HO-PCP acts as a high-

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

uncompetitive antagonist of the NMDA receptor via the

dizocilpine Dizocilpine (INN), also known as MK-801, is a pore blocker of the ''N''-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is ...

(MK-801) site (K_i = 30 nM). It has much higher affinity than PCP for this site (K_i = 250 nM, for comparison; 8-fold difference). The drug also has high affinity for the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

(MOR) (K_i = 39–60 nM) in animal test subjects, the

κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind op ...

(KOR) (K_i = 140 nM), and the sigma σ₁ receptor (K_i = 42 nM; IC₅₀ = 19 nM), whereas it has only low affinity for the

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

(K_i = 2,300 nM). The high affinity of 3-HO-PCP for

opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin ...

s is unique among arylcyclohexylamines and is in contrast to PCP, which has only very low affinity for the MOR (K_i = 11,000–26,000 nM; 282- to 433-fold difference) and the other opioid receptors (K_i = 4,100 nM for the KOR and 73,000 nM for the DOR). Although it was hypothesized that 3-HO-PCP might be a metabolite of PCP in humans, there is no evidence that this is the case.

Chemistry

3-HO-PCP is an

. Close analogues of 3-HO-PCP include PCP,

3-MeO-PCP 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 acts mainly as an NMDA receptor antagonist, though it has also be ...

4-MeO-PCP 4-Methoxyphencyclidine (methoxydine, 4-MeO-PCP) 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 r ...

3-MeO-PCMo 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 stimulatio ...

, and somewhat more distantly

ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ...

methoxyketamine Methoxyketamine or 2-MeO-2-deschloroketamine is a designer drug of the arylcyclohexylamine class first reported in 1963. It is an analog of ketamine in which the chlorine atom has been replaced with a methoxy group. Its synthesis by rearrangemen ...

3-MeO-PCE 3-Methoxyeticyclidine (3-MeO-PCE), also known as methoxieticyclidine, is a dissociative anesthetic that is qualitatively similar to PCE and PCP and has been sold online as a designer drug. On October 18, 2012 the Advisory Council on the Misus ...

methoxetamine Methoxetamine, abbreviated as MXE, is a dissociative hallucinogen that has been sold as a designer drug. It differs from many dissociatives such as ketamine and phencyclidine (PCP) that were developed as pharmaceutical drugs for use as general ...

and dimetamine.

Society and culture

Legal status

On October 18, 2012 the

Advisory Council on the Misuse of Drugs The Advisory Council on the Misuse of Drugs (ACMD) is a British statutory advisory non-departmental public body, which was established under the Misuse of Drugs Act 1971. Mandate Its terms of reference, according to the Act, are as follows: '' ...

in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the European mainland, continental mainland. It comprises England, Scotlan ...

released a report about

, saying that the "harms of methoxetamine are commensurate with Class B of the Misuse of Drugs Act (1971)", despite the fact that the act does not classify drugs based on harm. The report went on to suggest that all analogues of MXE should also become class B drugs and suggested a catch-all clause covering both existing and unresearched arylcyclohexamines, including 3-HO-PCP. 3-HO-PCP is banned in Sweden and Switzerland.

References

{{Sigma receptor modulators Arylcyclohexylamines Designer drugs Dissociative drugs NMDA receptor antagonists Opioid modulators Phenols 1-Piperidinyl compounds Sigma receptor ligands Synthetic opioids

Pharmacology

Chemistry

Society and culture

Legal status

See also

References