Mepacrine

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Structural formula
(±) -quinacrine enantiomers structural formulase.png
1: 1 mixture of ( R ) -form (top) and ( S ) -form (bottom)
General
Non-proprietary name Mepacrine
other names
  • Quinacrine
  • ( RS ) -6-chloro-9- (4-diethylamino-1-methylbutylamino) -2-methoxyacridine ( IUPAC )
  • Mepacrinum ( Latin )
Molecular formula C 23 H 30 ClN 3 O
External identifiers / databases
CAS number
  • 83-89-6
  • 69-05-6 (dihydrochloride)
EC number 201-508-7
ECHA InfoCard 100.001.371
PubChem 237
ChemSpider 232
DrugBank DB01103
Wikidata Q417208
Drug information
ATC code

P01 AX05

Drug class

Antiprotozoic

properties
Molar mass 399.96 g · mol -1
Physical state

firmly

Melting point

248-250 ° C (Di hydrochloride dihydrate)

pK s value

10.3

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302-315-319-335
P: 261-305 + 351 + 338
Toxicological data

50 mg kg −1 ( LD 50mouseiv )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Mepacrine is a drug that has historically been used for therapy and malaria prophylaxis . Mepacrine is still occasionally used today to treat Giardia infections.

development

The effect of acridine - derivatives as antiprotozoic had Paul Ehrlich in 1912 in the treatment of trypanosomiasis found in animal experiments. After the war, a large number of derivatives were tested for their effects on protozoal and bacterial infections in various laboratories. Mepacrine was discovered around 1930 by Walter Kikuth at IG Farbenindustrie in Elberfeld (Bayer) in a screening program of around 12,000 substances as a promising antimalarial agent. It was synthesized by the chemists Fritz Mietzsch and Hans Mauss at Bayer. Mepacrine was marketed under various trade names . It became known under the name Atebrin ® or (in the USA) Quinacrine (Atabrine ® ).

Mechanism of action

The mechanism of action of mepacrine is unclear; binding to DNA through intercalation may play a role. Mepacrine also acts as a FIASMA (functional inhibitor of acid sphingomyelinase ).

Historical meaning

The development of synthetic anti-malarials was of military importance, as it made it independent of the overseas supply of cinchona bark for quinine production . During the Second World War , mepacrine played no role on the German side, as even better drugs such as Sontochin , which is closely related to chloroquine , had been developed in the meantime .

On the part of the Allies, the production of mepacrine was considered to be important to the war effort, accordingly Imperial Chemical Industries in Great Britain and, from 1941 in the USA, the Winthrop company were commissioned to manufacture it. Under the name Quinacrine, mepacrine was the most important antimalarial drug used by the Allies in Southeast Asia. Improved remedies like chloroquine were only available after the end of the war. According to Walter Sneader, the war production of quinacrine and penicillin at the time was the cornerstone for the United States to become the largest pharmaceutical manufacturer in the world in the post-war period.

Todays use

Mepacrine is not approved as a medicinal product. In different countries it can be used for protozoan infections in human and veterinary medicine in individual cases with a special permit from the authorities.

literature

Individual evidence

  1. a b Entry on mepacrine in the DrugBank of the University of Alberta .
  2. a b Quinacrine dihydrochloride data sheet from Sigma-Aldrich , accessed on April 9, 2011 ( PDF ).
  3. Entry on mepacrine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  4. Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .