Jump to content

Bambuterol

From Wikipedia, the free encyclopedia
Bambuterol
Bambuterol (top),
and (R)-bambuterol (bottom)
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • Unknown
Routes of
administration
Oral (tablets)
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability20%
MetabolismExtensive hepatic.
Further metabolized to terbutaline by plasma cholinesterase
Elimination half-life13 hours (bambuterol)
21 hours (terbutaline)
ExcretionRenal
Identifiers
  • (RS)-5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diyl bis(dimethylcarbamate)
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H29N3O5
Molar mass367.446 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • O=C(Oc1cc(cc(OC(=O)N(C)C)c1)C(O)CNC(C)(C)C)N(C)C
  • InChI=1S/C18H29N3O5/c1-18(2,3)19-11-15(22)12-8-13(25-16(23)20(4)5)10-14(9-12)26-17(24)21(6)7/h8-10,15,19,22H,11H2,1-7H3 checkY
  • Key:ANZXOIAKUNOVQU-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Bambuterol (INN) is a long-acting β adrenoceptor agonist (LABA) used in the treatment of asthma; it also is a prodrug of terbutaline. Commercially, the AstraZeneca pharmaceutical company produces and markets bambuterol as Bambec and Oxeol.[1]

It is not available in the U.S.

Indications

[edit]

As other LABAs, bambuterol is used in the long-term management of persistent asthma.[1] It should not be used as a rescue medication for short-term relief of asthma symptoms.

Contraindications

[edit]

Bambuterol is contraindicated in pregnancy and in people with seriously impaired liver function. It can be used by people with renal impairment, but dose adjustments are necessary.[1]

Adverse effects

[edit]

The adverse effect profile of bambuterol is similar to that of salbutamol, and may include fatigue, nausea, palpitations, headache, dizziness and tremor.[1]

Interactions

[edit]

Concomitant administration of bambuterol with corticosteroids, diuretics, and xanthine derivatives (such as theophylline) increases the risk of hypokalemia (decreased levels of potassium in the blood).[2]

Bambuterol acts as a cholinesterase inhibitor, and can prolong the duration of action of suxamethonium (succinylcholine) and other drugs whose breakdown in the body depends on cholinesterase function.[1] Butyrylcholinesterase activity returns to normal approximately two weeks after bambuterol is stopped.[3] It can also enhance the effects of non-depolarizing neuromuscular blockers, such as vecuronium bromide.[2]

Synthesis

[edit]
Thieme ChemDrug Synthesis:[4] Patent:[5] Korean:[6] Sino:[7] Asymmetric:[8][9]

The reaction between 3',5'-Dihydroxyacetophenone [51863-60-6] (1) and Dimethylcarbamoyl chloride [79-44-7] (2) gives 5-Acetyl-1,3-phenylene bis(dimethylcarbamate) [81732-48-1] (3). Halogenation with bromine led to 5-(Bromoacetyl)-1,3-phenylene bis(dimethylcarbamate) [81732-49-2] (4). Treatment with N-(tert-Butyl)benzylamine [3378-72-1] (5) afforded [81732-47-0] (6). Catalytic hydrogenation completed the synthesis of bambuterol (7).

References

[edit]
  1. ^ a b c d e Sweetman SC, ed. (2009). "Bronchodilators and Anti-asthma Drugs". Martindale: The complete drug reference (36th ed.). London: Pharmaceutical Press. pp. 1115–16. ISBN 978-0-85369-840-1.
  2. ^ a b Sweetman (2009), pp. 1132–33.
  3. ^ Sitar DS (October 1996). "Clinical pharmacokinetics of bambuterol". Clinical Pharmacokinetics. 31 (4): 246–56. doi:10.2165/00003088-199631040-00002. PMID 8896942. S2CID 25696134.
  4. ^ Castaer, J.; Prous, J.; Bambuterol. Drugs Fut 1986, 11, 7, 553.
  5. ^ EP0043807 idem Otto Agne Olsson, et al. U.S. patent 4,419,364 (1983 to DRACO AB); CA, 96, 199263.
  6. ^ 김신종, et al. KR100803291 (2008).
  7. ^ 唐冬军 & 寇景平, CN104262202 (2016 to Guangdong HEC Pharmaceutical).
  8. ^ Asami, K., Machida, T., Jung, S., Hanaya, K., Shoji, M., Sugai, T. (December 2013). "Synthesis of (R)-bambuterol based on asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with incubated whole cells of Williopsis californica JCM 3600". Journal of Molecular Catalysis B: Enzymatic. 97: 106–109. doi:10.1016/j.molcatb.2013.08.003.
  9. ^ Cao, G., Hu, A., Zou, K., Xu, L., Chen, J., Tan, W. (July 2008). "Highly enantioselective synthesis, crystal structure, and circular dichroism spectroscopy of ( R )-bambuterol hydrochloride". Chirality. 20 (7): 856–862. doi:10.1002/chir.20558.