Dipipanone

Dipipanone

Systematic (IUPAC) name
4,4-Diphenyl-6-(1-piperidinyl)-heptan-3-one
Clinical data
Pregnancy cat.	?
Legal status	Schedule I (USA) CD Schedule 2 Class A (UK)
Routes	Oral, Intravenous
Identifiers
CAS number	467-83-4 Y
ATC code	None
PubChem	CID 13331
DrugBank	DB01491
ChemSpider	12766 Y
UNII	verifiedrevid = 399909836 X188638Y2V verifiedrevid = 399909836 N
Chemical data
Formula	C24H31NO
Mol. mass	349.52
SMILES	eMolecules & PubChem
InChI InChI=1S/C24H31NO/c1-3-23(26)24(21-13-7-4-8-14-21,22-15-9-5-10-16-22)19-20(2)25-17-11-6-12-18-25/h4-5,7-10,13-16,20H,3,6,11-12,17-19H2,1-2H3 Y Key:SVDHSZFEQYXRDC-UHFFFAOYSA-N Y
N(what is this?)

Dipipanone^[1] 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

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.^[2]

Usage

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. The UK, Ireland and South Africa are known to continue to use the substance but it is infrequently prescribed.

Chemistry

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 Other related compounds with equivalent activity where the piperidine ring has been replaced by other groups, include the morpholine derivative phenadoxone, as well as the corresponding pyrrolidine derivative.^[3] The general procedure for synthesis is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.^[4][5]

Medical use and recreational abuse

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.

References

1. ^ GB patent 654975, Peter Ofner, Eric Walton, "Improvements relating to the Synthesis of Diphenyl Ketones", published 1948-02-09, issued 1951-07-04 
2. ^ Fang, Glover, Jarman, Gorrod: Inhibition of monoamine oxidase B by dipipanone and cyclizine. Pharmaceutical Sciences (1995), 1(6), 295-296.
3. ^ Lenz GR, Evans SM, Walters DE, Hopfinger AJ. Opiates (1986). pp406-407. Academic Press. ISBN 978-0124438309
4. ^ P. A. J. Janssen, Synthetic Analgesics. Part 1. Diphenylpropylamines, 1960, Pergamon Press, NY
5. ^ Casy AF, Pargitt RY. Opioid analgesics, chemistry and receptors. 1986, Plenum Press, New York. ISBN 0306421305