Phencyclidine

Structural formula
General
Non-proprietary name	Phencyclidine
other names	1- (1-phenylcyclohexyl) piperidine Agent SN Sernyl
Molecular formula	C 17 H 25 N (phencyclidine) C 17 H 25 N HCl (phencyclidine hydrochloride )
External identifiers / databases
CAS number 77-10-1 (phencyclidine) 956-90-1 (phencyclidine hydrochloride) PubChem 6468 DrugBank DB03575 Wikidata Q407324
Drug information
Drug class	Anesthetics
properties
Molar mass	243.39 g · mol -1 (phencyclidine) 279.85 g · mol -1 (phencyclidine · hydrochloride)
Melting point	46-46.5 ° C (phencyclidine) 233–235 ° C (phencyclidine hydrochloride)
boiling point	135-137 ° C (133.3 Pa) (phencyclidine)
pK s value	8.29
safety instructions
GHS labeling of hazardous substances Hydrochloride danger H and P phrases H: 301 P: 301 + 310
Toxicological data	75 mg kg −1 ( LD 50 ,  mouse ,  oral , base) 2.8 mg kg −1 ( LD 50 ,  mouse ,  ip , base) 14 mg kg −1 ( LD Lo ,  human ,  oral , hydrochloride) 135 mg kg −1 ( LD 50 ,  rat ,  oral , hydrochloride)
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Phencyclidine (abbreviation of phen yl cycl ohexylpiper idin shortly PCP ) in the drug scene as Angel Dust (angel dust) , Londrea , Killerweed , Sherman Hemsley , TAC or Peace Pill known is as a drug -occupied Dissoziativum from the group of Arylcyclohexylamine . The company Parke-Davis developed it in 1956 originally as a drug of the class of anesthetic , but its marketing was soon due to an unfavorable risk-benefit ratio is set. Especially after long-term use there is a risk of psychological dependence. In animal experiments it damages the brain tissue . In Germany, phencyclidine is subject to the Narcotics Act and is not marketable.

pharmacology

Action profile

The exact mechanism of action of phencyclidine is unknown. Its effect is attributed to interactions with NMDA receptors , in which it blocks and inactivates the open channel (open channel blocker). This is a feature it shares with other dissociatives. In terms of this mode of action, phencyclidine is most similar to ketamine , but its effect is more psychotic and less analgesic (pain-relieving).

Side effects

The hallucinogenic effects of PCP are similar to the effects of LSD ; dissociative states such as nitrous oxide and ketamine also occur.

In connection with the use of phencyclidine, drowsiness, drowsiness, amnesia , perception disorders, speech and coordination disorders, motor disorders (especially eye rolling, gait disorders), salivation, hallucinations and aggressiveness up to fits of rage with harm to oneself and others with simultaneous insensitivity to pain were observed become. PCP induces a state of intoxication that is said to be similar to that of the acute schizophrenic flare-up. PCP not only triggers the typical schizophrenic positive symptoms (e.g. delusion, hallucinations, ego disorders), but also negative symptoms (e.g. apathy , alogy , impoverishment of affect, anhedonia ). Fear also occurs in the form of nightmarish psychotic episodes ( bad trip ). With high doses of PCP, seizures and ultimately death from respiratory depression can occur.

Neurotoxicity

Damage to the nervous system can occur, especially with prolonged use. Phencyclidine, like other NMDA blockers , can cause brain damage. Phencyclidine is more toxic and more complex in its toxicity than other dissociatives. The damage affects several brain regions and is probably mediated via different receptor systems.

Long-term use

After frequent use of phencyclidine, schizophrenia-like states with memory loss, a burn-out feeling, paranoia , confusion, aggressiveness and uncontrolled hallucinations - even without taking the drug - were observed for days . It is not clear whether this is caused by phencyclidine deposits in adipose tissue and the brain (depot effect) or the neurotoxicity of this substance.

Interactions

The mixed consumption of phencyclidine and alcohol can intensify effects and cause hallucinations, fainting , respiratory depression and respiratory arrest with itching.

metabolism

About 80% of the phencyclidine is hydroxylated in the 4-position of the rings in the human organism and excreted in the urine as glucuronide . In the hydroxylation also arises N cyclohexyl N -phenyl-5-aminopentanoic. The hydroxylated metabolite has no psychoactive effect. A small part of the remaining 20% ​​of the phencyclidine is split oxidatively to phenylcyclohexamine .

Countermeasures in the event of an acute overdose / the outbreak of (temporary) drug psychosis

There is no known antidote that releases phencyclidine from its receptor bonds, so countermeasures are purely symptomatic. Usually the patient is fixed in order to exclude aggressive and possibly dangerous actions towards himself and others. Thereafter, a fast-acting and highly potent neuroleptic (often haloperidol ) is usually administered intravenously to reduce the delusions and aggression. The patient is then sedated , usually with medium-acting benzodiazepines . In most cases, the consumer has to remain under in-patient surveillance for several days, as “ flashbacks ” can occur, which represent a renewed danger for him and his environment.

chemistry

Phencyclidine hydrochloride in its pure form is a white crystalline powder ("angel dust"). PCP is chemically related to the anesthetic ketamine . Derivatives: tenocyclidine , eticyclidine , rolicyclidine .

proof

Evidence is provided by a modified version of the Scott test . Like all other tertiary phencyclidines, PCP reacts with Marquis reagent to form a red color complex. This is followed by thin-layer chromatography for the separation into the pure substances with coupled spectral analysis, which under UV light makes two peaks at λ = 257 nm and λ = 261 nm and two partial shoulders at λ = 252 nm and λ = 266 nm visible.

synthesis

The synthesis takes place in two steps. First, cyclohexanone 1 and piperidine 2 react to form an enamine 3 . A Grignard reaction with phenylmagnesium bromide then produces phencyclidine 4 . The first synthesis took place in 1926 by Kötz and Merkel.

An alternative is the Strecker synthesis with potassium cyanide to form α- aminonitrile and a subsequent Grignard reaction. Mechanistically speaking, the loss of the cyanide ion produces an iminium ion , which is then attacked by the Grignard reagent. The reaction is known as the Bruylants reaction .

Use as an intoxicant

PCP, both in crystalline form and dissolved in water

Phencyclidine is primarily used as a recreational drug in the United States . The locally limited demand there is covered by illegal production, which is comparatively cheap. Phencyclidine is used as a powder or in dissolved form, particularly nasally ("sniffing in"), orally (swallowing) or inhalatively (smoking). Plant material impregnated with phencyclidine (including cannabis , mint, etc., so-called “hogs” or “Shermans”) is also used for smoking.

history

The basis for the production of phencyclidine was laid in 1926 by a study by Arthur Kötz and Paul Merkel, who reported on the reaction of the related compound 1-piperidinocyclohexanecarbonitrile (PCC) with Grignard compounds. After the sedative effect of phencyclidine had been successfully tested on monkeys, phencyclidine was marketed as an animal anesthetic in 1956 in Germany under the trade name Sernylan (CI-395) by Parke Davis and Co. In 1963 it was approved as a dissociative anesthetic under the brand name Sernyl for use on humans, but was withdrawn from the market four years later due to its strong psychological side effects. To date, it is approved for veterinary use in the United States.

It first appeared in the drug scene in 1967 at a rock festival in San Francisco and was initially forgotten because of its incorrectly declared effect. Due to its effectiveness as an intoxicant, its use as an animal anesthetic was also banned. In 1977 the substance reappeared in the US armed forces stationed in Germany and from there it was spread in underground laboratories that made modifications to the molecular structure in order to enhance the hallucinogenic effect. More than 125 phencyclidine derivatives are currently known.

Phencyclidine probably also played a role in the massacre at the Grover Cleveland Elementary School in San Diego (1979, known from the related Bob Geldof song I don't like Mondays ): the perpetrator Brenda Ann Spencer claims to have been during their Amok tat have been under the influence of phencyclidine. According to the prosecution, she was sober during the act.

In the United States and South Africa , phencyclidine was manufactured as a chemical weapon ( psychological warfare agent ) under the names Agent SN and EA 2148 .

literature

• Karl-Artur Kovar : Designer drugs from the phencyclidine range. Pharmacy in our time . 23rd year 1994
• Richard Seymour: The New Drugs. Look-Alikes, Drugs of Deception and Designer Drugs. San Francisco 1989.

Web links

Commons : Phencyclidine  - Collection of pictures, videos and audio files

• PCP . In: Erowid . (English)
• Drug scouts via PCP
• ChemSub Online: Phencyclidine

Individual evidence

1. ^ ^{A b c} The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 1246, ISBN 978-0-911910-00-1 .
2. ↑ ^{a b c} Entry on phencyclidine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
3. ↑ ^{a b} Datasheet Phencyclidine hydrochloride from Sigma-Aldrich , accessed on April 18, 2011 ( PDF ).
4. ↑ ^{a b} Entry on phencyclidine hydrochloride in the ChemIDplus database of the United States National Library of Medicine (NLM) .
5. ↑ ^{a b c d e f g h} T. Velocity: Intoxicating drugs: Market forms and modes of action . Springer-Verlag, 2013. ISBN 9783662096819 . P. 68.
6. ↑ FH Meyers, E. Jawetz, A. Goldfien: Textbook of Pharmacology: For students of medicine of all study stages and for doctors . Springer-Verlag, 2013. ISBN 9783642661839 . P. 59.
7. ↑ Heinz Lüllmann, Klaus Mohr: Pharmacology and Toxicology . Georg Thieme Verlag, 2006. ISBN 9783133685160 . P. 356.
8. ↑ R. Nakki et al. (1995): Cerebellar toxicity of phencyclidine . In: J. Neurosci. Vol. 3, pp. 2097-2108. PMID 7891155 .
9. ↑ FR Sharp et al. (1994): Neuronal injury produced by NMDA antagonists can be detected using heat shock proteins and can be blocked with antipsychotics . In: Psychopharmacol Bull , Vol. 30, pp. 555-560. PMID 7770620 .
10. ^ Daniel Trachsel, Nicolas Richard: Psychedelic chemistry: Aspects of psychoactive molecules. Schwabe AG, 2015. ISBN 9783037882368 .
11. ↑ Felix Tretter: Addiction medicine compact: Addictive diseases in clinic and practice. Schattauer Verlag, 2012. ISBN 9783794528660 . P. 250.
12. ↑ A. Kötz, Paul Merkel: On the knowledge of hydroaromatic alkamines. In: Journal for Practical Chemistry. 113, 1926, p. 49, doi : 10.1002 / prac.19261130107 .
13. ↑ AT Shulgin, DE MacLean: Illicit Synthesis of Phencyclidine (PCP) and Several of its Analogs. In: Clinical Toxicology. 9, 2008, p. 553, doi : 10.3109 / 15563657608988157 .
14. ↑ Wolfram Keup: Biology of Addiction . Springer-Verlag, 2013, ISBN 978-3-642-82542-2 , p. 313 ( limited preview in Google Book search).
15. ↑ 'I Don't Like Mondays' . In: Boomtown Rats.co.uk . 2003. Archived from the original on February 14, 2012. Retrieved on February 29, 2012., with details about the case.
16. ↑ Background: I Don't Like Mondays (Bob Geldof) . In: The Mudcat Cafe (forum) . Retrieved February 29, 2012.
17. ^ ^{A b} Reid Kirby: Paradise Lost: The Psycho Agents. (PDF; 379 kB) The CBW Conventions Bulletin, Issue 71, p. 2, May 2006.
18. ↑ ^{a b} Chandre Gould, Peter I. Folb, Robert Berold (ed.): Project Coast: Apartheid's Chemical and Biological Warfare Program. United Nations Publications UNIDIR, 2002, p. 92, ISBN 978-9290451440 .

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