Nicomorphine

Structural formula
General
Non-proprietary name	Nicomorphine
other names	(5 α , 6 α ) -7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol-3,6-di-3-pyridinecarboxylate; Morphine bis (pyridine-3-carboxylate); 3,6-dinicotinoylmorphine; 3,6-DNM; Morphine dinicotinate;
Molecular formula	C 29 H 25 N 3 O 5
External identifiers / databases
EC number	211-357-9
ECHA InfoCard	100.010.326
PubChem	5362460
ChemSpider	4515048
Wikidata	Q7030497
Drug information
ATC code	N02 AA04
Drug class	Opioid - analgesic
properties
Molar mass	495.54 g · mol -1 (nicomorphine)
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
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Nicomorphine is a semi-synthetically produced opioid with strong analgesic (pain-relieving) effectiveness. Nicomorphine acts as a pure agonist on the μ-opioid receptor . Structurally, it is a diester of morphine with two molecules of nicotinic acid .

history

Nicomorphine was developed as a powerful analgesic in 1957. It has been regulated by the Single Convention on Narcotic Drugs since 1961 (Group 2). In Germany it is a non-marketable narcotic drug .

chemistry

Extraction and presentation

Nicomorphine was first produced semi-synthetically from morphine in 1959.

Ball and stick model of nicomorphine

pharmacology

effect

As an opioid, nicomorphine has the same profile of effects and side effects, and thus essentially the same risk potential as other opioids. It is a prodrug of morphine . Due to its higher lipophilicity, it has a faster onset of action than morphine.

Side effects

Side effects can occur with nicomorphine that exceed the pre-existing tolerance to opioids due to the pre-consumption. These are tiredness, sleep disturbances , 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 .

Nicomorphine has an effect on the fetus when taken during pregnancy.

Pharmacokinetics

After intravenous administration nicomorphine has a plasma half-life of three minutes and is metabolized in the bloodstream and the liver to form the pharmacologically active metabolites morphine and 6-nicotinylmorphine . The morphine has a plasma half-life of 135–190 minutes, nicotinylmorphine 3 to 15 minutes.

With epidural use, it is detectable for about an hour and a half. The duration of action is 18.2 ± 10.1 hours. The plasma half-life is the same as with intravenous administration, except that nicomorphine is slowly released into the bloodstream.

After rectal administration of nicomorphine, morphine can be detected in the serum after eight minutes and has a plasma half-life of 1.48 ± 0.48 hours. In the intestine, the metabolic products of morphine, morphine-3 and morphine-6-glucoronides, are broken down after 12 minutes with a plasma half-life of 2.8 hours for both. No 6-mononicotinylmorphine is formed. The bioavailability of morphine and its active metabolites is 88%. No nicomorphine can be detected in the urine.

When administered intramuscularly , the plasma half-life is 0.32 ± 0.20 hours, with slow release to the bloodstream. The plasma half-life of 6-mononicotinylmorphine is also about 0.39 ± 0.09, indicating release as a rate-limiting step. Morphine has a plasma half-life of 1.38 ± 0.31 hours. Morphine is metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The plasma half-life for both glucuronides is about 2.6 hours (p = 0.07). No 6-mononicotinylmorphine is formed. The bioavailability corresponds to that of intravenous administration.

Trade names

Trade names for nicomorphine are e.g. B. Vilan ( A ; a. H .: CH , DK ), MorZet ( NL , a. H.).

literature

The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals . 15th edition. Merck & Co., Whitehouse Station NJ 2013, ISBN 978-1-849736-70-1 , p. 1213.

Individual evidence

↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
^ Thomas Nordegren: The AZ Encyclopedia of Alcohol and Drug Abuse. Universal-Publishers, 2002, ISBN 978-1-581-12404-0 , p. 463.
↑ Appendix I to the German Narcotics Act .
↑ Herman H. Waldvogel: Analgesics Antinociceptives Adjuvants. Springer-Verlag, 2013, ISBN 978-3-642-56710-0 , p. 289 ( limited preview in the Google book search).
↑ Herman H. Waldvogel: Analgesics Antinociceptives Adjuvants. Springer-Verlag, 2013, ISBN 978-3-642-97649-0 , pp. 292, 427.
↑ Koopman-Kimenai, PM, Vree TB, Booij, LH, Dirksen, R, Nijhuis, GM: Pharmacokinetics of intravenously administered nicomorphine and its metabolites in man. . In: European Journal of Anesthesiology . 10, No. 3, England, March 1, 1993, pp. 125-132. PMID 8462537 .
↑ Koopman-Kimenai PM, Vree TB, Hasenbos MA, Weber EW, Verweij-Van Wissen CP, Booij LH: Pharmacokinetics of nicomorphine and its metabolites in man after epidural administration. (Dutch) . In: Pharmaceutish Weekblad. Scientific Edition. . 13, No. 3, Netherlands, June 21, 1991, pp. 142-147. PMID 1923705 .
↑ PM Koopman-Kimenai, TB Vree, LH Booij, R. Dirksen: Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates. In: Pharmacy world & science: PWS. Volume 16, Number 6, December 1994, pp. 248-253, PMID 7889023 .
↑ PM Koopman-Kimenai, TB Vree, LH Booij, R. Dirksen: The bioavailability of intramuscularly administered nicomorphine (Vilan) with its metabolites and their glucuronide conjugates in surgical patients. In: International journal of clinical pharmacology and therapeutics. Volume 33, Number 8, August 1995, pp. 442-448, PMID 8556223 .

[NV-1] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[Nordegren-2] Thomas Nordegren: The AZ Encyclopedia of Alcohol and Drug Abuse. Universal-Publishers, 2002, ISBN 978-1-581-12404-0 , p. 463.

[3] Appendix I to the German Narcotics Act .

[4] Herman H. Waldvogel: Analgesics Antinociceptives Adjuvants. Springer-Verlag, 2013, ISBN 978-3-642-56710-0 , p. 289 ( limited preview in the Google book search).

[Waldvogel-5] Herman H. Waldvogel: Analgesics Antinociceptives Adjuvants. Springer-Verlag, 2013, ISBN 978-3-642-97649-0 , pp. 292, 427.

[NicoIV-6] Koopman-Kimenai, PM, Vree TB, Booij, LH, Dirksen, R, Nijhuis, GM: Pharmacokinetics of intravenously administered nicomorphine and its metabolites in man. . In: European Journal of Anesthesiology . 10, No. 3, England, March 1, 1993, pp. 125-132. PMID 8462537 .

[NicoEpidural-7] Koopman-Kimenai PM, Vree TB, Hasenbos MA, Weber EW, Verweij-Van Wissen CP, Booij LH: Pharmacokinetics of nicomorphine and its metabolites in man after epidural administration. (Dutch) . In: Pharmaceutish Weekblad. Scientific Edition. . 13, No. 3, Netherlands, June 21, 1991, pp. 142-147. PMID 1923705 .

[NicoRectal-8] PM Koopman-Kimenai, TB Vree, LH Booij, R. Dirksen: Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates. In: Pharmacy world & science: PWS. Volume 16, Number 6, December 1994, pp. 248-253, PMID 7889023 .

[9] PM Koopman-Kimenai, TB Vree, LH Booij, R. Dirksen: The bioavailability of intramuscularly administered nicomorphine (Vilan) with its metabolites and their glucuronide conjugates in surgical patients. In: International journal of clinical pharmacology and therapeutics. Volume 33, Number 8, August 1995, pp. 442-448, PMID 8556223 .