Bambuterol

Indications

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

Contraindications

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.

Adverse effects

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

Interactions

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).

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. It can also enhance the effects of non-depolarizing neuromuscular blockers, such as vecuronium bromide.

Synthesis

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

References

1. (2009). "[[Martindale: The complete drug reference]]". Pharmaceutical Press.
2. Sweetman (2009), pp. 1132–33.
3. (October 1996). "Clinical pharmacokinetics of bambuterol". Clinical Pharmacokinetics.
4. Castaer, J.; Prous, J.; Bambuterol. Drugs Fut 1986, 11, 7, 553.
5. EP0043807 idem Otto Agne Olsson, et al. {{US patent. 4419364 (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.