Desoxypipradrol: Difference between revisions

{{Short description|Chemical compound}}

{{Use dmy dates|date=January 2015}}

| Watchedfields = changed

| verifiedrevid = 447738657

| chirality = [[Racemic mixture]]

| tradename =

| legal_DE = Anlage II

| legal_UK = Class B

| routes_of_administration = [[Oral administration|By mouth]], nasal and sublingual

| metabolism = Liver

| elimination_half-life = 16–20 hours

| CAS_number_Ref = {{cascite|correct|CAS}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 49UNK1BV8T

| smiles = C1(C(C2NCCCC2)C3=CC=CC=C3)=CC=CC=C1

'''Desoxypipradrol''', also known as '''2-⁠diphenylmethylpiperidine''' ('''2-DPMP'''), is a drug developed by Ciba in the 1950s<ref>US Patent 2820038 - 2-Diphenyl-Methyl-Piperidine</ref> which acts as a [[norepinephrine-dopamine reuptake inhibitor]] (NDRI).<ref name="Ferris RM 1979">{{cite journal | vauthors = Ferris RM, Tang FL | title = Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l-[3H]norepinephrine and [3H]dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 210 | issue = 3 | pages = 422–8 | date = September 1979 | pmid = 39160 }}</ref>

==Chemistry==

Desoxypipradrol is closely related on a [[chemical structure|structural]] level to the compounds [[methylphenidate]] and [[pipradrol]], all three of which share a similar [[pharmacological]] [[mechanism of action|action]].<ref name="Ferris RM 1979"/> Of these three [[piperidine]]s, desoxypipradrol has the longest elimination [[half-life]], as it is a highly [[lipophilic]] [[molecule]] lacking [[Chemical polarity|polar]] [[functional group]]s that are typically targeted by [[metabolic]] [[enzyme]]s, giving it an extremely long duration of action when compared to most psychostimulants. Methylphenidate, on the other hand, is a short-acting compound, as it possesses a [[methyl]]-[[ester]] [[Moiety (chemistry)|moiety]] that is easily cleaved, forming a highly polar [[acid]] group, while pipradrol is intermediate in duration, possessing a [[hydroxyl]] group which can be [[Xenobiotic conjugation|conjugated]] (e.g. with [[glucuronide]]) to increase its [[hydrophilicity]] and facilitate [[excretion]], but no easily metabolized groups.

==History==

Desoxypipradrol was developed by the pharmaceutical company CIBA (now called [[Novartis]]) in the 1950s,<ref>{{cite journal | vauthors = Tripod J, Sury E, Hoffmann K | title = [Analeptic effect of a new piperidine derivative] | journal = Experientia | volume = 10 | issue = 6 | pages = 261–2 | date = June 1954 | pmid = 13183068 | doi = 10.1007/BF02157398 | s2cid = 20091456 }}</ref> and researched for applications such as the treatment of [[narcolepsy]] and [[ADHD]]; however, it was dropped from development after the related drug methylphenidate was developed by the same company. Methylphenidate was felt to be the superior drug for treating ADHD due to its shorter duration of action and more predictable [[pharmacokinetics]], and while desoxypipradrol was researched for other applications (such as facilitation of rapid recovery from [[anaesthesia]]<ref>{{cite journal | vauthors = Bellucci G | title = [(2-Diphenylmethyl-piperidine hydrochloride and the methyl ester of 2-chloro-2-phenyl-2-(2-piperidyl)-acetic acid), drugs with waking effect in anesthesia] | journal = Minerva Anestesiologica | volume = 21 | issue = 6 | pages = 125–8 | date = June 1955 | pmid = 13244387 }}</ref>), its development was not continued. The hydroxylated derivative [[pipradrol]] was, however, introduced as a clinical drug indicated for [[Major depressive disorder|depression]], [[narcolepsy]] and cognitive enhancement in organic [[dementia]].

== Detection in biological specimens ==

Desoxypipradrol may be quantitated in [[blood]], [[Blood plasma|plasma]] or [[urine]] by liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma desoxypipradrol concentrations are expected to be in a range of 10–50&nbsp;μg/L in persons using the drug recreationally, >100&nbsp;μg/L in intoxicated patients and >600&nbsp;μg/L in victims of acute overdosage.<ref>{{cite book | author = Baselt RC | title = Disposition of toxic drugs and chemicals in man | year = 2014 | publisher = Biomedical Publications | location = Seal Beach, Ca. | isbn = 978-0-9626523-9-4 | pages = 2172–2173 }}</ref>

==Legal status==

Desoxypipradrol's structural similarity to [[pipradrol]] makes it possible that it would be considered a [[Federal Analog Act|controlled substance analogue]] in several countries such as [[Australia]] and [[New Zealand]].

===China===

As of October 2015 2-DPMP is a controlled substance in China.<ref>{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | publisher=China Food and Drug Administration | date=27 September 2015 | language=Chinese | access-date=1 October 2015 | archive-date=1 October 2015 | archive-url=https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html | url-status=dead }}</ref>

===United Kingdom===

As of 4 November 2010, the [[UK]] [[Home Office]] announced a ban on the importation of 2-DPMP, following a recommendation from the [[ACMD]].<ref>[http://www.homeoffice.gov.uk/media-centre/news/drug-import-ban Import ban on psychoactive drug] UK Home Office</ref>

Prior to the import ban, desoxypipradrol was sold as a 'legal high' in several products, most notably "Ivory wave". Its use lead to several [[Emergency Department]] visits which prompted the [[UK government]] to commission a review from the [[ACMD]]. One man had ingested nearly 1&nbsp;gram of the drug which may have been fatal without sedation with an anaesthetic dose of a benzodiazepine administered in accident and emergency.{{Citation needed|date=March 2011}}

The Advisory Council on the Misuse of Drugs stated in their report<ref name="ACMD's comments">{{cite web | url = http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/acmd1/advice-ivory-wave?view=Standard&pubID=840140 | title = ACMD advice on 'Ivory Wave' | access-date = 2012-03-11 | date = 2012-01-27 | format = PDF | publisher = UK Home Office | archive-url = http://webarchive.nationalarchives.gov.uk/20111208173726/http%3A//www.homeoffice.gov.uk/publications/alcohol%2Ddrugs/drugs/acmd1/advice%2Divory%2Dwave?view%3DStandard%26pubID%3D840140 | archive-date = 8 December 2011 | url-status = dead }}</ref> that:

2-DPMP was due to become a class B drug<ref name="draft legislation">{{cite web | url = http://www.legislation.gov.uk/ukdsi/2012/9780111520857/memorandum/contents | title = The Misuse of Drugs Act 1971 (Amendment) Order 2012 | access-date = 2012-03-11 | date = 2012-01-27 | format = PDF | publisher = UK Home Office}}</ref> on 28 March 2012,<ref>{{cite web | url = http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/2-dpmp-compounds/D2PM?view=Binary | title = Government accepts ACMD's advice to schedule D2PM, 2-DPMP and phenzepam | access-date = 2012-03-11 | date = 2012-01-27 | format = PDF | publisher = UK Home Office}}</ref> but the bill was scrapped as two steroids deemed not to be abusable were included in the bill but were later recommended to remain uncontrolled.<ref>{{cite web | url = http://www.homeoffice.gov.uk/publications/agencies-public-bodies/acmd1/acmd-steroids-advice-2012?view=Standard&pubID=1007793 | title = ACMD letter on further advice on the classification of two steroidal substances - February 2012 | access-date = 2012-03-18 | date = 2012-02-14 | format = PDF | publisher = UK Home Office}}</ref> There was a new discussion about its fate on April 23, 2012, where it was decided that the bill would be rewritten and 2-DPMP would still be banned. It was also decided that the bill would be a blanket ban of related chemicals.<ref name="debate">{{cite web | url = https://publications.parliament.uk/pa/cm201012/cmgeneral/deleg1/120423/120423s01.htm | title = Draft Misuse of Drugs Act 1971 (Amendment) Order 2012 | access-date = 2012-05-04 | date = 2012-04-23 | publisher = UK Home Office}}</ref>

Desoxypipradrol was eventually made a class B drug and placed in Schedule I on 13 June 2012.<ref name="control 2dpmp">{{cite web | url = http://homeoffice.gov.uk/about-us/corporate-publications-strategy/home-office-circulars/circulars-2012/014-2012/ | title = A Change to the Misuse of Drugs Act 1971: control of pipradrol-related compounds and phenazepam | access-date = 2012-07-30 | date = 7 Jun 2012 | publisher = UK Home Office}}</ref> There were no recorded deaths from the drug between the banning of its import and the banning of its possession. "Esters and ethers of pipradrol" were controlled with the same amendment as class C drugs.<ref name="control 2dpmp"/>

{{div col|colwidth=30em}}

* [[Diphenyl-2-pyridylmethane]]

* [[Diphenidine]], a dissociative anaesthetic (NMDAR antagonist)

{{div col end}}

{{Monoamine reuptake inhibitors}}

[[Category:Norepinephrine–dopamine reuptake inhibitors]]

[[Category:2-Piperidinyl compounds]]

[[Category:Designer drugs]]

[[Category:Benzhydryl compounds]]