Pethidine

Structural formula
General
Non-proprietary name	Pethidine
other names	1-methyl-4-phenylpiperidine-4-carboxylic acid ethyl ester ( IUPAC ) Pethidinum ( Latin ) Isonipecaine
Molecular formula	C 15 H 21 NO 2 C 15 H 21 NO 2 HCl (pethidine hydrochloride )
Brief description	white, crystalline powder (pethidine hydrochloride)
External identifiers / databases
CAS number 57-42-1 50-13-5 ( hydrochloride ) PubChem 4058 DrugBank DB00454 Wikidata Q55434
Drug information
ATC code	N02 AB02
Drug class	Opioid - analgesic
properties
Molar mass	247.33 g · mol -1 283.8 g · mol -1 (· pethidine hydrochloride )
Melting point	30 ° C 187–190 ° C (pethidine hydrochloride)
pK s value	8.59
solubility	Pethidine hydrochloride is very easily soluble in water and easily soluble in ethanol 96%
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Hydrochloride danger H and P phrases H: 301 P: 301 + 310
Toxicological data	162 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Pethidine or meperidine ( also known as meperidine in the USA ) is the oldest fully synthetic opioid . It was first synthesized in July 1937 by Otto Schaumann and Otto Eisleb at IG Farben ( Hoechst plant ). In 1939 the morphine - like piperidine derivative (in the form of the hydrochloride salt ) was launched for medical use under the trade name Dolantin . While pethidine lost importance in Germany with the advent of newer preparations, it is still one of the most important strong analgesics worldwide . The structure of pethidine is a simplified replica of the atropine molecule .

synthesis

Pethidine 3 can be prepared in a two-step synthesis. In the first step, starting from benzyl cyanide 1 and bis (chloroethyl) methylamine 2, in the presence of sodium amide, the cyclization to the piperidine ring takes place . The ester is then formed from the nitrile function .

pharmacology

Pethidine is an agonist at the µ-receptors , its effect, side effects and interactions are therefore quite similar to morphine . However, there are some relevant differences and special features in contrast to morphine:

1. Pethidine forms the active metabolite norpethidine by demethylation on nitrogen , which accumulates in the body and can trigger seizures . Pethidine is therefore only suitable as an analgesic for acute pain, not for long-term therapy.
2. Pethidine is more likely to cause tachycardia than bradycardia .
3. Pethidine is significantly more effective than morphine or piritramide for postoperative shivering , which can be used in postoperative pain therapy.
4. The duration of action is rather short for an opioid with 2 to a maximum of 4 hours.

After intravenous administration, the maximum effect is reached within 3–10 minutes, after intramuscular administration within 20–40 minutes. Oral (as a drop) or rectal (as a suppository ) application is also possible with good bioavailability . Pethidine and its metabolites are mainly excreted via the kidneys. Since pethidine only has a 0.1 to 0.2-fold morphine potency , the usual single dose is 50–100 mg i. m. or 25-50 mg i.d. v. It can be repeated after 3–6 hours, but a daily dose of 500 mg should not be exceeded. In contrast to other opioids, which can trigger a sphincter oddi (papilla vateri), pethidine is used in the pain therapy of colic in cholelithiasis .

Analytics

For the reliable determination of the qualitative Pethidins at pharmacodynamic or forensic problems is the coupling of mass spectrometry with the gas chromatography and the Liquidchromatographie used. Blood, serum, plasma, urine , fingernails, toenails or hair can be used as test material after adequate sample preparation .

Legal status in Germany

Police ordinance on the dispensing of Dolantin in pharmacies of June 4, 1940

In the Federal Republic of Germany, pethidine is a marketable and prescription narcotic due to its listing in Appendix 3 of the BtMG . Handling without permission or prescription is generally punishable.

Trade names

Alodan (A), Demerol (USA), Dolantin (D), Pethidine (D, CH)

literature

• Specialist information Dolantin
• E. Burgius: Intensive course in general and special pharmacology. Urban & Fischer, Munich / Jena 2001, ISBN 3-437-42611-7 .
• RXList: Demerol

Individual evidence

1. ↑ European Pharmacopoeia Commission (Ed.): European Pharmacopoeia 5th Edition . tape 5.0-5.8 , 2006.
2. ↑ Entry on pethidine. In: Römpp Online . Georg Thieme Verlag, accessed on June 7, 2014.
3. ↑ European Pharmacopoeia. 6th edition. Deutscher Apotheker Verlag, Stuttgart 2008, ISBN 978-3-7692-3962-1 , pp. 3620-3621.
4. ↑ ^{a b} Entry on pethidine in the ChemIDplus database of the United States National Library of Medicine (NLM)
5. ↑ European Pharmacopoeia, 8th edition, Grundwerk 2014, p. 4509.
6. ↑ ^{a b} Data sheet Meperidine hydrochloride from Sigma-Aldrich , accessed on April 18, 2011 ( PDF ).
7. ↑ Volker Schulz, Rudolf Hänsel: Rational Phytotherapy - Advice for medical practice. 3. Edition. Springer Verlag, 1996, ISBN 3-540-61240-8 .
8. ↑ Patent Appl. DE 679 281 IG Farben 1937.
9. ↑ K. Eckart, J. Röhrich, D. Breitmeier, M. Ferner, R. Laufenberg-Feldmann, R. Urban: Development of a new multi-analyte assay for the simultaneous detection of opioids in serum and other body fluids using liquid chromatography -tandem mass spectrometry. In: J Chromatogr B Analyt Technol Biomed Life Sci. 1001, Sep 15, 2015, pp. 1-8. PMID 26241181
10. ↑ M. Ramírez Fernández Mdel, F. Van Durme, SM Wille, V. di Fazio, N. Kummer, N. Samyn: Validation of an automated solid-phase extraction method for the analysis of 23 opioids, cocaine, and metabolites in urine with ultra-performance liquid chromatography-tandem mass spectrometry. In: J Anal Toxicol. 38 (5), Jun 2014, pp. 280-288. PMID 24790061
11. ^ I. Shu, J. Jones, M. Jones, D. Lewis, A. Negrusz: Detection of Drugs in Nails: Three Year Experience. In: J Anal Toxicol. 39 (8), Oct 2015, pp. 624-628. PMID 26378136
12. ↑ K. Aleksa, P. Walasek, N. Fulga, B. Kapur, J. Gareri, G. Koren: Simultaneous detection of seventeen drugs of abuse and metabolites in hair using solid phase micro extraction (SPME) with GC / MS. In: Forensic Sci Int. 218 (1-3), May 10, 2012, pp. 31-36. PMID 22047752

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