Zopiclone

from Wikipedia, the free encyclopedia
Structural formula
Zopiclone Enantiomers Structural Formulase.png
1: 1 mixture of stereoisomers : ( R ) form (top) and ( S ) form (bottom)
General
Non-proprietary name Zopiclone
other names
  • [(5 RS ) -6- (5-chloropyridin-2-yl) -7-oxo-6,7-dihydro-5 H -pyrrolo [3,4-b] pyrazin-5-yl] (4-methylpiperazin- 1-carboxylate) ( IUPAC )
  • ( RS ) -4-methylpiperazine-1-carboxylic acid 6- (5-chloropyridin-2-yl) -7-oxo-6,7-dihydro-5 H -pyrrolo [3,4- b ] pyrazin-5-yl ester
  • DL -4-methylpiperazine-1-carboxylic acid 6- (5-chloropyridin-2-yl) -7-oxo-6,7-dihydro-5 H -pyrrolo [3,4- b ] pyrazin-5-yl ester
  • (±) -4-methylpiperazine-1-carboxylic acid 6- (5-chloropyridin-2-yl) -7-oxo-6,7-dihydro-5 H -pyrrolo [3,4- b ] pyrazin-5-yl ester
  • rac -4-methylpiperazine-1-carboxylic acid 6- (5-chloropyridin-2-yl) -7-oxo-6,7-dihydro-5 H -pyrrolo [3,4- b ] pyrazin-5-yl ester
Molecular formula C 17 H 17 ClN 6 O 3
External identifiers / databases
CAS number 43200-80-2
EC number 256-138-9
ECHA InfoCard 100.051.018
PubChem 5735
DrugBank DB01198
Wikidata Q220426
Drug information
ATC code

N05 CF01

Drug class

Hypnotic Sedative Tranquilizer

properties
Molar mass 388.81 g · mol -1
Physical state

Solid

Melting point

178 ° C

pK s value

-1.5; 6.8

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 08 - Dangerous to health

Caution

H and P phrases H: 302-312-315-319-332-335-361
P: 261-280-305 + 351 + 338
Toxicological data

827 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 .

Zopiclone is a drug from the cyclopyrrolone group of active ingredients . Zopiclone has a sleep-inducing effect in small doses - in high doses it forces sleep. It also has an anxiolytic , anticonvulsant and muscle relaxant effect . The active ingredient was approved in Germany in March 1994.

pharmacology

From a chemical point of view, zopiclone is a cyclopyrrolone derivative, which is the only approved sedative of the cyclopyrrolones. In terms of its action profile, it belongs to the group of so-called GABA receptor agonists; it acts on the same receptors that are otherwise activated by the inhibitory neurotransmitter GABA. Pharmacologically, it is classified as a new generation sedative - as a Z-drug  .

Pharmacokinetics

After oral ingestion, zopiclone is rapidly absorbed and absorbed into the central nervous system . The maximum plasma concentration of 0.02–0.06 µg / ml is reached after just one hour . The bioavailability is 80%. Zopiclone binds to the α1 subunit of the GABA receptor . This significantly increases the sleep-promoting effect of the neurotransmitter γ-aminobutyric acid at the same concentration. This reinforcement at the GABA receptor occurs primarily locally in the cerebral cortex and cerebellum , but not in other peripheral receptor systems. The half-life is 5 hours.

The two main metabolites

Side effects

The most common side effect described is the irritation of the sense of taste (bitter, metallic taste). In addition, dry mouth, headache, daytime tiredness and a general feeling of weakness were observed as side effects. Furthermore, anterograde amnesia can occur, which means a memory gap after taking medication. Confusion , visual disturbances , dizziness and unconsciousness have also been reported in some cases . If taken regularly over several weeks, withdrawal symptoms must be expected upon discontinuation. Zopiclone is psychologically and physically addictive . For this reason, it should not be prescribed for more than two weeks. Use in people with a pre-existing addiction disorder is only indicated in exceptional cases .

Stereoisomerism

Zopiclone is chiral and therefore contains a stereocenter. There are thus two enantiomers , the ( R ) form and the ( S ) form. Only ( S ) -zopiclone ( eszopiclone ) is pharmacologically active.

Both the racemate (1: 1 mixture of enantiomers) and the pure eszopiclone are used medicinally .

Trade names

Imovane (D, CH), Optidorm (D), Somnal (A), Somnosan (D), Ximovan (D), Zopiclodura (D), Zopitin (CZ), various generics (D)

The pure ( S ) -zopiclone (eszopiclone) is only approved in the USA as a sleep aid under the name Lunesta .

Web links

Individual evidence

  1. ↑ a b c d e Zopiclone data sheet at Sigma-Aldrich , accessed on April 26, 2011 ( PDF ).
  2. ↑ Entry on zopiclone. In: Römpp Online . Georg Thieme Verlag, accessed on June 30, 2019.
  3. ↑ Topic: Medicines> Package Insert. Package insert for ZOPICLON AL 7.5 film-coated tablets. In: Apotheken-Umschau . Retrieved April 26, 2020 .
  4. ↑ Why sleeping pills are so dangerous. In: NDR.de. January 13, 2017, accessed June 24, 2020 .
  5. ↑ World Health Organization - Assessment of Zopiclone (PDF; 199 kB).
  6. ↑ Otto Benkert: Compendium of psychiatric pharmacotherapy. Springer Science & Business Media, 2009, ISBN 978-3-540-78470-8 , p. 399 ( limited preview in Google book search).
  7. ↑ Levke Sonntag: The importance of the newer hypno-sedatives zopiclone and zolpidem in the clinical-toxicological test material with special consideration of the classic benzodiazepines . (PDF; 1.91 MB) Dissertation, Hamburg 2009.
  8. ↑ FDA approved labeling text for LUNESTA ® (eszopiclone) (PDF; 180 kB) 2008.