Desoxypipradrol

Desoxypipradrol, also known as 2-⁠diphenylmethylpiperidine (2-DPMP), is a drug developed by Ciba in the 1950s[1] which acts as a norepinephrine-dopamine reuptake inhibitor (NDRI).[2]

Desoxypipradrol
Clinical data
Routes of
administration		By mouth, nasal and sublingual
ATC code
  • none
Legal status
Legal status
  • DE: Anlage II (Authorized trade only, not prescriptible)
  • UK: Class B
Pharmacokinetic data
Bioavailability>90%
MetabolismLiver
Elimination half-life16-20 hours
Identifiers
IUPAC name
  • (RS)-2-benzhydrylpiperidine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.007.525
Chemical and physical data
FormulaC18H21N
Molar mass251.373 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
SMILES
  • C1(C(C2NCCCC2)C3=CC=CC=C3)=CC=CC=C1
InChI
  • InChI=1S/C18H21N/c1-3-9-15(10-4-1)18(16-11-5-2-6-12-16)17-13-7-8-14-19-17/h1-6,9-12,17-19H,7-8,13-14H2 Y
  • Key:RWTNXJXZVGHMGI-UHFFFAOYSA-N Y
  (verify)

Chemistry

Desoxypipradrol is closely related on a structural level to the compounds methylphenidate and pipradrol, all three of which share a similar pharmacological action.[2] Of these three piperidines, desoxypipradrol has the longest elimination half-life, as it is a highly lipophilic molecule lacking polar functional groups that are typically targeted by metabolic enzymes, 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 that is easily cleaved, forming a highly polar acid group, while pipradrol is intermediate in duration, possessing a hydroxyl group which can be 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,[3] 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[4]), its development was not continued. The hydroxylated derivative pipradrol was, however, introduced as a clinical drug indicated for depression, narcolepsy and cognitive enhancement in organic dementia.

Detection in biological specimens

Desoxypipradrol may be quantitated in blood, 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 μg/L in persons using the drug recreationally, >100 μg/L in intoxicated patients and >600 μg/L in victims of acute overdosage.[5]

Desoxypipradrol's structural similarity to pipradrol makes it possible that it would be considered a 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.[6]

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.[7]

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 gram of the drug which may have been fatal without sedation with an anaesthetic dose of a benzodiazepine administered in accident and emergency.

The Advisory Council on the Misuse of Drugs stated in their report[8] that:

"there are serious harms associated with 2-DPMP... typically prolonged agitation (lasting up to 5 days after drug use which is sometimes severe, requiring physical restraint), paranoia, hallucinations and myoclonus (muscle spasms/twitches)."

2-DPMP was due to become a class B drug[9] on 28 March 2012,[10] 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.[11] 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.[12]

Desoxypipradrol was eventually made a class B drug and placed in Schedule I on 13 June 2012.[13] 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.[13]

See also

References
  1. US Patent 2820038 - 2-Diphenyl-Methyl-Piperidine
  2. Ferris RM, Tang FL (September 1979). "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". The Journal of Pharmacology and Experimental Therapeutics. 210 (3): 422–8. PMID 39160.
  3. Tripod J, Sury E, Hoffmann K (June 1954). "[Analeptic effect of a new piperidine derivative]". Experientia. 10 (6): 261–2. doi:10.1007/BF02157398. PMID 13183068. S2CID 20091456.
  4. Bellucci G (June 1955). "[(2-Diphenylmethyl-piperidine hydrochloride and the methyl ester of 2-chloro-2-phenyl-2-(2-piperidyl)-acetic acid), drugs with waking effect in anesthesia]". Minerva Anestesiologica. 21 (6): 125–8. PMID 13244387.
  5. Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, Ca.: Biomedical Publications. pp. 2172–2173. ISBN 978-0-9626523-9-4.
  6. "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015.
  7. Import ban on psychoactive drug UK Home Office
  8. "ACMD advice on 'Ivory Wave'". UK Home Office. 27 January 2012. Archived from the original (PDF) on 8 December 2011. Retrieved 11 March 2012.
  9. "The Misuse of Drugs Act 1971 (Amendment) Order 2012" (PDF). UK Home Office. 27 January 2012. Retrieved 11 March 2012.
  10. "Government accepts ACMD's advice to schedule D2PM, 2-DPMP and phenzepam" (PDF). UK Home Office. 27 January 2012. Retrieved 11 March 2012.
  11. "ACMD letter on further advice on the classification of two steroidal substances - February 2012" (PDF). UK Home Office. 14 February 2012. Retrieved 18 March 2012.
  12. "Draft Misuse of Drugs Act 1971 (Amendment) Order 2012". UK Home Office. 23 April 2012. Retrieved 4 May 2012.
  13. "A Change to the Misuse of Drugs Act 1971: control of pipradrol-related compounds and phenazepam". UK Home Office. 7 June 2012. Retrieved 30 July 2012.
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