Meclozin

Structural formula
( S ) -form (top) and ( R ) -form (bottom), 1: 1 stereoisomeric mixture
General
Non-proprietary name	Meclozin
other names	Meclizine ( RS ) -1 - [(4-chlorophenyl) phenylmethyl] -4 - [(3-methylphenyl) methyl] piperazine ( IUPAC )
Molecular formula	C 25 H 27 ClN 2 [( RS ) -Meclozine] C 25 H 27 ClN 2 · 2HCl [( RS ) -Meclozin · dihydrochloride] C 25 H 27 ClN 2 · 2HCl · 2H 2 O [( RS ) -Meclozin · dihydrochloride · monohydrate]
External identifiers / databases
CAS number 569-65-3 [( RS ) -Meclozin] 1104-22-9 [( RS ) -Meclozin · dihydrochloride] 31884-77-2 [( RS ) -Meclozin · dihydrochloride · monohydrate] PubChem 4034 DrugBank DB00737 Wikidata Q386441
Drug information
ATC code	R06 AE05
Drug class	Antihistamines
properties
Molar mass	390.95 g · mol -1 [( RS ) -Meclozin] 463.88 g · mol -1 [( RS ) -Meclozin · dihydrochloride] 481.90 g · mol -1 [( RS ) -Meclozin · · dihydrochloride monohydrate]
Physical state	firmly
Melting point	206–216 ° C with decomposition (racemate dihydrochloride)
boiling point	230 ° C
pK s value	3.1; 6.2
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 Caution H and P phrases H: 302-361 P: 281
Toxicological data	625 mg kg −1 ( LD 50 ,  mouse ,  im ) 1650 mg kg −1 ( LD 50 ,  mouse ,  oral ) 1750 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 .

Meclozine is a drug selected from the group of systemic H ₁ - antihistamines . It works against nausea and vomiting and experience has shown that it can also be used safely during pregnancy . However, it has not been on the market in Germany since 2007 (former trade name : Postadoxin N ^® ). In other EU countries, preparations are or were known under the name Postafene or Agyrax .

synthesis

The synthesis of meclozine starts from (4-chlorophenyl) phenylmethanol, which is first converted to a 4-chlorophenylphenylpiperazinylmethane intermediate after halogenation by means of thionyl chloride and reaction with acetylpiperazine. After the acetyl group has been split off under acidic conditions, N -alkylation takes place on the piperazine ring with 3-methylbenzyl chloride to give the racemic target molecule.

Alternatively, the last synthesis step can be carried out as a reductive N -alkylation on the piperazine ring with 3-methylbenzaldehyde .

The racemate is formed during the synthesis . For pharmaceutical applications, the compound is converted into the dihydrochloride.

Clinical information

Meclozin is used for nausea and vomiting , especially for motion sickness and vomiting during pregnancy .

The safety for use during pregnancy has been well documented and it is even considered the drug of choice for vomiting. An alternative is doxylamine , among others .

Pharmacological properties

Meclozin works by competitive inhibition of histamine H ₁ receptors . Since it crosses the blood-brain barrier as a first-generation antihistamine , it is not only antiemetic , but also makes you tired.

Stereoisomerism

Meclozin contains a stereogenic center and is chiral . The drug is used as a racemate {1: 1 mixture of ( R ) -1 - [(4-chlorophenyl) phenylmethyl] -4 - [(3-methylphenyl) methyl] piperazine and ( S ) -1 - [(4- Chlorophenyl) phenylmethyl] -4 - [(3-methylphenyl) methyl] piperazine} is used.

Individual evidence

1. ↑ M. Brandstätter Kuhnert, R. Hoffmann, M. Senn: Thermo-Microscopic and Spectrophotometric Determination of Anti Histamines and Related Compounds , in: Microchem® J . , 1963 , 7 , pp. 357-374.
2. ↑ ^{a b c} Entry on meclozin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
3. ^ Entry on meclozin. In: Römpp Online . Georg Thieme Verlag, accessed on January 14, 2019.
4. ↑ ^{a b} Data sheet Meclizine dihydrochloride, ≥97% (HPLC) from Sigma-Aldrich , accessed on October 31, 2016 ( PDF ).
5. ^ ^{A b c} A. Kleemann, J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications , 4th edition, Thieme 2001, ISBN 3-13-115134-X .
6. ↑ J.-H. Fuhrkop, G. Li: Organic Synthesis - Concepts and Methods , Wiley-VCH 2003, p. 237, ISBN 978-3-527-30272-7 .
7. ↑ US 2,709,169 (UCB, 1955).
8. ↑ Källén B, Mottet I: Delivery outcome after the use of meclozine in early pregnancy . In: European Journal of Epidemiology . 18, No. 7, 2003, pp. 665-669. PMID 12952140 . Retrieved September 17, 2010.
9. ↑ ANTIEMETIC THERAPY FOR PREGNANCY SUCCESS at arznei-telegramm.de .
10. ↑ Embryotox: drug safety during pregnancy and lactation: Database drugs and active ingredients: Meclozin .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !