Ketobemidone

Structural formula
General
Non-proprietary name	Ketobemidone
other names	1- [4- (3-Hydroxyphenyl) -1-methylpiperidin-4-yl] -1-propanone; [4- (3-hydroxyphenyl) -1-methyl-4-piperidyl] ethyl ketone; 1- [4- (3-hydroxyphenyl) -1-methyl-4-piperidinyl] -1-propanone; 4- ( m -hydroxyphenyl) -1-methyl-4-piperidyl ethyl ketone;
Molecular formula	C 15 H 21 NO 2
Brief description	White, crystalline powder (ketobemidone hydrochloride)
External identifiers / databases
EC number	207-421-0
ECHA InfoCard	100.006.748
PubChem	10101
ChemSpider	9697
DrugBank	DB06738
Wikidata	Q2471714
Drug information
ATC code	N02 AB01
Drug class	Opioid - analgesic
properties
Molar mass	247.34 g · mol -1
Melting point	156-157 ° C ; 201–202 ° C (hydrochloride);
solubility	soluble in water , soluble in ethanol (hydrochloride)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
Toxicological data	10 mg kg −1 ( LD 50 , rat , iv ) ; 14 mg kg −1 ( LD 50 , mouse , iv ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Ketobemidone (also cetobemidone ) is a fully synthetic opioid from the group of pethidines with a strong analgesic effect. Ketobemidone is a morphine - like piperidine derivative and a pure agonist at the μ-opioid receptor .

description

Ketobemidone was patented in 1947 and 1948 as a strong analgesic by Ciba ( Cliradon ) and also by Winthrop and IG Farben . In the Federal Republic of Germany, ketobemidone is a marketable but not a prescription narcotic due to its listing in Annex II to Section 1 (1) of the BtMG .

chemistry

structure

Dissolved ketobemidone exists in two conformers with an equatorial or axial position of the phenyl ring on the piperidine ring . The latter is considered to be the active conformation that acts on the receptor.

Extraction and presentation

Ketobemidone is produced fully synthetically.

Another synthetic route starts from 3-methoxybenzyl cyanide, which condenses with N , N- bis (2-chloroethyl) - N -methylamine in the presence of the strong base sodium amide to give the methylpiperidine derivative, which reacts with the Grignard reagent methylmagnesium bromide to form an intermediate, which after Cleavage with hydrobromic acid leads to ketobemidone.

pharmacology

effect

As an opioid, ketobemidone has the same profile of effects and side effects, and thus essentially the same risk potential as other opioids. Ketobemidone has an analgesic potency of 1 to 2 and works for four to five hours with a single dose of 5 to 15 mg.

Side effects

These are tiredness, insomnia , drowsiness , nausea , vomiting , edema in the legs, urinary retention , constipation and pruritus . They usually go away as tolerance develops or the dose is reduced. Sleep and sexual disorders last the longest .

Use during pregnancy and breastfeeding: Ketobemidone has an effect on the fetus when taken during pregnancy.

Trade names

Monopreparations : Cliradon (except for trade), Ketodur, Ketogan Novum, Ketorax

literature

Hermann PT Ammon et al .: Hunnius Pharmaceutical Dictionary . 9th edition, Walter de Gruyter Verlag , Berlin - New York, 2004, ISBN 3-11-017475-8 geb. and ISBN 3-11-017487-1 brosch., p. 327.
Römpp Lexikon Chemie , Georg Thieme Verlag , Stuttgart - New York, 1997, p. 649 f.
The Merck Index, 15th edition, The Royal Society of Chemistry 2013, ISBN 978-1-84973-670-1 , pp. 982 f.

Individual evidence

^ Q. Alan Xu, Timothy L. Madden: Analytical Methods for Therapeutic Drug Monitoring and Toxicology . John Wiley & Sons, 2011, ISBN 0-470-92279-6 , pp. 267 ( limited preview in Google Book search).
↑ ^a ^b ^c ^d ^e entry on cetobemidone. In: Römpp Online . Georg Thieme Verlag, accessed on July 3, 2016.
^ J. Elks: The Dictionary of Drugs: Chemical Data, Chemical Data, Structures and Bibliographies . Springer, 2014, ISBN 978-1-4757-2085-3 , pp. 467 ( limited preview in Google Book search).
↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 7.0, ketobemidine hydrochloride. Loose-leaf collection, 23rd delivery 2011, Wissenschaftliche Verlagsgesellschaft Stuttgart.
↑ Eberhard Klaschik : Pain therapy and symptom control in palliative medicine. In: Stein Husebø , Eberhard Klaschik (ed.): Palliative medicine. 5th edition, Springer, Heidelberg 2009, ISBN 3-642-01548-4 , pp. 207-313, here: p. 234.

[Q._Alan_Xu,_Timothy_L._Madden-1] Q. Alan Xu, Timothy L. Madden: Analytical Methods for Therapeutic Drug Monitoring and Toxicology . John Wiley & Sons, 2011, ISBN 0-470-92279-6 , pp. 267 ( limited preview in Google Book search).

[RömppOnline-2] ↑ ^a ^b ^c ^d ^e entry on cetobemidone. In: Römpp Online . Georg Thieme Verlag, accessed on July 3, 2016.

[J._Elks-3] J. Elks: The Dictionary of Drugs: Chemical Data, Chemical Data, Structures and Bibliographies . Springer, 2014, ISBN 978-1-4757-2085-3 , pp. 467 ( limited preview in Google Book search).

[NV-4] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[5] K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 7.0, ketobemidine hydrochloride. Loose-leaf collection, 23rd delivery 2011, Wissenschaftliche Verlagsgesellschaft Stuttgart.

[6] Eberhard Klaschik : Pain therapy and symptom control in palliative medicine. In: Stein Husebø , Eberhard Klaschik (ed.): Palliative medicine. 5th edition, Springer, Heidelberg 2009, ISBN 3-642-01548-4 , pp. 207-313, here: p. 234.