Bambuterol

Bambuterol
	Bambuterol (top),; and (R)-bambuterol (bottom)
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy; category	Unknown;
Routes of; administration	Oral (tablets)
ATC code	R03CC12 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	20%
Metabolism	Extensive hepatic.; Further metabolized to terbutaline by plasma cholinesterase
Elimination half-life	13 hours (bambuterol); 21 hours (terbutaline)
Excretion	Renal
Identifiers
	IUPAC name (RS)-5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diyl bis(dimethylcarbamate);
CAS Number	81732-65-2 ; HCl: 81732-46-9 ;
PubChem CID	54766;
IUPHAR/BPS	6601;
DrugBank	DB01408 ;
ChemSpider	49466 ;
UNII	Y1850G1OVC; HCl: 786Q84QZ3F ;
KEGG	D07377 ;
ChEBI	CHEBI:553827 ;
ChEMBL	ChEMBL521589 ;
CompTox Dashboard (EPA)	DTXSID5048550 ;
Chemical and physical data
Formula	C18H29N3O5
Molar mass	367.446 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES O=C(Oc1cc(cc(OC(=O)N(C)C)c1)C(O)CNC(C)(C)C)N(C)C;
	InChI 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 ; Key:ANZXOIAKUNOVQU-UHFFFAOYSA-N ;
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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]

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]

^ ^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.
^ ^a ^b Sweetman (2009), pp. 1132–33.
^ Sitar DS (October 1996). "Clinical pharmacokinetics of bambuterol". Clinical Pharmacokinetics. 31 (4): 246–56. doi:10.2165/00003088-199631040-00002. PMID 8896942. S2CID 25696134.
^ Castaer, J.; Prous, J.; Bambuterol. Drugs Fut 1986, 11, 7, 553.
^ EP0043807 idem Otto Agne Olsson, et al. U.S. patent 4,419,364 (1983 to DRACO AB); CA, 96, 199263.
^ 김신종, et al. KR100803291 (2008).
^ 唐冬军 & 寇景平, CN104262202 (2016 to Guangdong HEC Pharmaceutical).
^ 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.
^ 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.

[Martindale-1] 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.

[Martindale2-2] Sweetman (2009), pp. 1132–33.

[Sitar-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.

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