Dipipanone

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Dipipanone
Dipipanone2DACS.svg
Dipipanone3DanJH.gif
Systematic (IUPAC) name
4,4-diphenyl-6-(1-piperidinyl)-heptan-3-one
Clinical data
Trade names Diconal
Legal status
Routes Oral
Pharmacokinetic data
Metabolism Liver-mediated
Half-life 3.5 hours[1]
Identifiers
CAS number 467-83-4 N
ATC code None
PubChem CID 13331
DrugBank DB01491
ChemSpider 12766 YesY
UNII X188638Y2V YesY
Chemical data
Formula C24H31NO 
Mol. mass 349.52
 N (what is this?)  (verify)

Dipipanone (Pipadone)[2] is a strong opioid analgesic drug, used for very severe pain in cases where other analgesics are unsuitable, for instance where morphine is indicated but cannot be used due to the patient being allergic to morphine.

Dosage forms[edit]

The main preparation of the drug commercially available is mixed with cyclizine (Diconal, Wellconal) which has the advantage of reducing nausea, vomiting and histamine release associated with strong opioid therapy.[3]

Dipipanone was also available as an oral mixture 10 mg/5ml without the cyclizine during the 1970s - 1980's in the United Kingdom. This form was rare and used normally only in drug trials and in specialist diconal addiction clinics.

With the exception of oxycodone, dipipanone is now the only alternative opioid left to use in the UK that is of equal strength to morphine that can be prescribed instead. All the other opioids are either weaker like codeine, dihydrocodeine and pethidine or stronger like hydromorphone, oxymorphone, and fentanyl.

One of the biggest disadvantages on using dipipanone is that it is only produced in one dosage form that is mixed with the anti-emetic cyclizine at a ratio of 25% dipipanone to 75% cyclizine which limits the dose of dipipanone to an absolute maximum of 3 tablets per dose up to 4-6 times a day.

As of November 2011 Amdipharm stopped making the Diconal brand tablets for the UK due to undisclosed commercial reasons. However the product is listed as available on the manufacturer's website as of July 1, 2014. [4]General practitioners are now advised to prescribe it as generic dipipanone/cyclizine tablets.

Usage[edit]

Dipipanone is now unavailable in most countries of the world either by laws prohibiting its medicinal use as in the United States or by falling out of production as more modern analgesics took its market share. Great Britain, Northern Ireland and South Africa are known to continue to use the substance but it is infrequently prescribed.

Dipipanone is a Schedule I controlled substance in the United States; is has been assigned the ACSCN of 9622 and in 2013 had an annual manufacturing quota of 5 grammes.[5]

Chemistry[edit]

Chemically, dipipanone belongs to the class of opioids called the 4,4-diphenylheptane-3-ones. It closely resembles methadone, the only structural difference being the N,N-dimethyl moiety of methadone being replaced with a piperidine ring. Other related compounds with equivalent activity where the piperidine ring has been replaced by other groups, include the morpholine derivative phenadoxone, as well as the corresponding pyrrolidine derivative.[6] The general procedure for synthesis is illustrated by nucleophilic attack of diphenylacetonitrile on 2-chloro-1-piperidyl-propane. The resulting aminonitrile is then converted to the ethyl ketone with ethyl magnesium bromide by way of the ketimine which is hydrolyzed by cold aqueous acid.[7][8]

Medical and recreational use[edit]

Prescription of dipipanone is discouraged apart from in exceptional circumstances, because of the perceived risk of abuse - the BNF marks the substance as "less suitable for prescribing" along with other older compounds such as pethidine and pentazocine with unusual abuse patterns. The combination with cyclizine leads to a very strong "rush" if the drug is injected, however the tablets contain insoluble binders which led to many limb amputations and some fatalities (as with temazepam). During the late 1970s to early 1980s in the UK, many deaths were blamed on misuse of this preparation. As supplies became unavailable, opiate users would mix crushed methadone tablets or Physeptone ampoules with crushed Valoid (a cyclizine containing antihistamine) tablets, in an attempt to replicate the effect of Diconal.

See also[edit]

References[edit]

  1. ^ Paterson, S (April 1992). "Pharmacokinetics of dipipanone after a single oral dose." (PDF). British Journal of Clinical Pharmacology 33 (4): 449–50. doi:10.1111/j.1365-2125.1992.tb04066.x. PMC 1381337. PMID 1349495. 
  2. ^ GB patent 654975, Peter Ofner, Eric Walton, "Improvements relating to the Synthesis of Diphenyl Ketones", published 1948-02-09, issued 1951-07-04 
  3. ^ Fang, Glover, Jarman, Gorrod: Inhibition of monoamine oxidase B by dipipanone and cyclizine. Pharmaceutical Sciences (1995), 1(6), 295-296.
  4. ^ "Amdipharm Mercury Company Ltd.". http://www.amcolimited.com/products/amdipharm-spc. Amdipharm Mercury Company Ltd. Retrieved 1 July 2014. 
  5. ^ http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0703_2.htm
  6. ^ Lenz GR, Evans SM, Walters DE, Hopfinger AJ. Opiates (1986). pp406-407. Academic Press. ISBN 978-0-12-443830-9
  7. ^ P. A. J. Janssen, Synthetic Analgesics. Part 1. Diphenylpropylamines, 1960, Pergamon Press, NY
  8. ^ Casy AF, Pargitt RY. Opioid analgesics, chemistry and receptors. 1986, Plenum Press, New York. ISBN 0-306-42130-5