Clobutinol

Clobutinol is a cough suppressant formerly distributed by Boehringer Ingelheim and its licensees under the names Lomisat and Silomat, by Bioter as Biotussin, and by Violani-Farmavigor as Pertoxil. It has been withdrawn from the market worldwide.

Clobutinol
Clinical data
Trade namesBiotussin, Lomisat, Pertoxil, Silomat
AHFS/Drugs.comInternational Drug Names
Routes of
administration		oral
ATC code
Legal status
Legal status
  • Withdrawn
(EU)
Identifiers
IUPAC name
  • (RS)-1-(4-chlorophenyl)-4-dimethylamino-2,3-dimethyl-butan-2-ol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.035.373
Chemical and physical data
FormulaC14H22ClNO
Molar mass255.79 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
SMILES
  • Clc1ccc(cc1)CC(O)(C)C(C)CN(C)C
InChI
  • InChI=1S/C14H22ClNO/c1-11(10-16(3)4)14(2,17)9-12-5-7-13(15)8-6-12/h5-8,11,17H,9-10H2,1-4H3 Y
  • Key:KVHHQGIIZCJATJ-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Side effects and withdrawal

Side effects include drozwsiness, dizziness, insomnia, nausea, vomiting, and abdominal discomfort.[1] Studies in 2004 had indicated that clobutinol has the potential to prolong the QT interval.[2] Clobutinol was in 2007 determined to cause cardiac arrhythmia in some patients.[3]

Boehringer Ingelheim products containing clobutinol were voluntarily withdrawn from sale in Germany, and the rest of the world, on August 31, 2007.[4]

The approval for Germany and the EU was revoked in 2008.[5]

Prior to withdrawal, it was available throughout Europe and Central America, as well as in South Africa. Trade names include Biotussin, Lomisat (Spain), Pertoxil (Italy), and in most of the world, Silomat.[6]

Synthesis
Patents:[7][8]

The Mannich reaction of 2-butanone (1) with formaldehyde and dimethylamine gives 4-Dimethylamino-3-methyl-2-butanone [22104-62-7] (2). Grignard reaction with 4-chlorobenzylchloride [104-83-6] (3) afforded clobutinol (4).

See also

References
  1. Schlesser JL (1991). Drugs Available Abroad, 1st Edition. Derwent Publications Ltd. p. 29. ISBN 0-8103-7177-4.
  2. Bellocq C, Wilders R, Schott JJ, Louérat-Oriou B, Boisseau P, Le Marec H, et al. (November 2004). "A common antitussive drug, clobutinol, precipitates the long QT syndrome 2". Molecular Pharmacology. 66 (5): 1093–102. doi:10.1124/mol.104.001065. PMID 15280442.
  3. "Clobutinol-haltige Arzneimittel: BfArM ordnet Widerruf der Zulassung an". BfArM (German Federal Institute for Drugs and Medical Devices). 2007-08-31. Archived from the original on 2012-04-01. Clobutinol: BfArM orders cancellation of approval
  4. "Boehringer Ingelheim voluntarily withdraws its clobutinol containing medications". Boehringer Ingelheim. 2007-08-31. Archived from the original on 2012-01-27.
  5. "Cancellation of approval" (PDF). BfArM (German Federal Institute for Drugs and Medical Devices). 2008-06-06. Archived from the original (pdf) on 2012-04-01. Die Zulassungen für die o.g. Arzneimittel werden mit sofortiger Wirkung widerrufen.
  6. Schlesser JL (1991). Drugs Available Abroad, 1st Edition. Derwent Publications Ltd. p. 29. ISBN 0-8103-7177-4.
  7. GB898010 idem Alex Berg, U.S. Patent 3,121,087 (1962, 1964 both to Thomae).
  8. Dipl-Chem Dr Alex Berg, DE 1153380 (1963 to Thomae GmbH Dr K).
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.