Levosalbutamol as alternative to drugs on the basis of racemic salbutamol: Review of the results of pre-clinical research

Keywords: R-salbutamol, β2-agonist, chirality, enantioselectivity, pharmacodynamics


The aim of the work is to conduct an analytical review of the results of preclinical studies of levosalbutamol. The review discusses the pharmacodynamic features of the R-stereoisomer of salbutamol in vitro. The chemical bases of interaction of levosalbutamol with β2-adrenoreceptors, intracellular signaling cascades associated with β2-adrenoreceptors, and structural features of clinically significant ligands of β2-adrenoreceptors are presented. Broncholytic activity, influence on the contractility of the diaphragmatic muscles, mucociliary clearance of R-salbutamol in comparison with racemic salbutamol are described. The data presented indicate that all known β2-adrenergic receptor-dependent effects of racemic salbutamol, including bronchodilation, are realized by its R-enantiomer. There is evidence that the regular inhalation administration of racemic salbutamol is accompanied by a partial decrease in the bronchoprotective effect and an increase in airway hyperreactivity in response to the action of provocative factors. It was found that the development of hyperreactivity of the respiratory tract is excluded in the case of regular inhalation of levosalbutamol. Possible mechanisms of the paradoxical bronchoconstrictor effect of the salbutamol dystomer are described. This article shows the beneficial effect of levosalbutamol on mucociliary clearance, its anti-inflammatory activity and antiallergic effect. The image data are compared between the enantiomers and the racemate of salbutamol. Special attention is paid to the pharmacokinetics of enantiomers of salbutamol. The data presented from the preclinical studies provide evidence of chiral inversion of stereoisomers of salbutamol. 


Agrawal, D., Ariyarathna, K., & Kelbe, P. (2004). S-Albuterol activates pro-constrictory and pro-inflammatory pathways in human bronchial smooth muscle cells. Journal of Allergy and Clinical Immunology, 113(3), 503–510.

Ameredes, B. T., & Calhoun, W. J. (2006). R-Albuterol for asthma: Pro [a.k.a. S-Albuterol for Asthma: Con]. American Journal of Respiratory and Critical Care Medicine, 174, 965–974.

Ameredes, B. T., & Calhoun, W. J. (2010). Albuterol enantiomers: Pre-clinical and clinical value? Frontiers in Bioscience (Elite Edition), 2, 1081–1092.

Angulo, M., Taranto, E., Soto, J. P., Malacrida, L., Nin, N., Hurtado, F. J., & Píriz, H. (2009). Salbutamol improves diaphragmatic contractility in chronic airway obstruction. Archivos de Bronconeumología, 45(5), 230–234.

Arrowsmith, J. (2011). Trial watch: Phase II failures: 2008–2010. Nature Reviews Drug Discovery, 10(5), 328–329.

Arrowsmith, J. (2011). Trial watch: Phase III and submission failures: 2007–2010. Nature Reviews Drug Discovery, 10(2), 87.

Arroyo, M., Couëtil, L., Nogradi, N., Kamarudin, M., & Ivester, K. (2016). Efficacy of inhaled levalbuterol compared to albuterol in horses with recurrent airway obstruction. Journal of Veterinary Internal Medicine, 30(4), 1333–1337.

Auais, A., Wedde-Beer, K., & Piedimonte, G. (2005). Anti-inflammatory effect of albuterol enantiomers during respiratory syncytial virus infection in rats. Pediatric Pulmonology, 40(3), 228–234.

Auclair, В., Wainer, I., Fried, К., Koch, Р., Jerussi, Т., & Ducharme, М. (2000). A population analysis of nebulized (R)-albuterol in dogs using a novel mixed gut-lung absorption PK-PD model. Pharmaceutical Research, 17(10), 1228–1235.

Bae, R., Arteaga, A., Raj, J., & Ibe, B. (2012). Albuterol isomers modulate platelet-activating factor synthesis and receptor signaling in human bronchial smooth muscle cells. International Archives of Allergy and Immunology, 158(1), 18–26.

Baramki, D., Koester, J., Anderson, A., & Borish, L. (2002). Modulation of T-cell function by R- and S-isomers of albuterol: Anti-inflammatory influences of R-isomers are negated in the presence of the S-isomer. The Journal of Allergy and Clinical Immunology, 109(3), 449–454.

Barnette, D., Johnson, B., Pouncey, D., Nshimiyimana, R., Desrochers, L., Goodwin, T., & Miller, G. (2017). Stereospecific metabolism of R- and S-warfarin by human hepatic cytosolic reductases. Drug Metabolism and Disposition, 45(9), 1000–1007.

Berger, W. E. (2003). Levalbuterol: Pharmacologic properties and use in the treatment of pediatric and adult asthma. Annals of Allergy, Asthma and Immunology, 90(6), 583–591.

Blin, O. (2004). Chiral switch: Towards a better benefit-risk ratio? Therapie, 59(6), 625–628.

Bosak, A., Knežević, A., Gazić, S. I., Šinko, G., & Kovarik, Z. (2017). Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity. Journal of Enzyme Inhibition and Medicinal Chemistry, 32(1), 789–797.

Boskabady, M. H., & Aslani, M. R. (2007). Influence of epithelium on β-adrenoceptor desensitization of guinea pig tracheal smooth muscle. Respiratory Physiology and Neurobiology, 156(1), 69–78.

Bosmann, M., Grailer, J., Zhu, K., Matthay, M., Sarma, J., Zetoune, F., & Ward, P. (2012). Anti-inflammatory effects of β2 adrenergic receptor agonists in experimental acute lung injury. The FASEB Journal, 26(5), 2137–2144.

Boulton, D. W., & Fawcett, J. P. (2001). The pharmacokinetics of levosalbutamol: What are the clinical implications? Clinical Pharmacokinetics, 40(1), 23–40.

Boulton, D. W., & Fawcett, J. P. (2002). Β2-agonist eutomers: A rational option for the treatment of asthma? American Journal of Respiratory Medicine, 1(5), 305–311.

Broadley, K. J. (2006). Β-adrenoceptor responses of the airways: For better or worse? European Journal of Pharmacology, 533(1–3), 15–27.

Buchheit, K. H., Hofmann, A., & Fozard, J. R. (1995). Salbutamol-induced airway hyperreactivity in guinea pigs is not due to a loss of its bronchodilator effect. European Journal of Pharmacology, 287(1), 85–88.

Burke, D., & Henderson, D. J. (2002). Chirality: A blueprint for the future. British Journal of Anaesthesia, 88(4), 563–576.

Calcaterra, A., & D’Acquarica, I. (2017). The market of chiral drugs: Chiral switches versus de novo enantiomerically pure compounds. Journal of Pharmaceutical and Biomedical Analysis, S0731–7085(17), 31483-31488.

Cazzola, М., Page, С., Calzetta, L., & Matera, G. (2012). Pharmacology and therapeutics of bronchodilators. Pharmacological Reviews, 64, 450–504.

Chong, L., Suvarna, K., Chess-Williams, R., & Peachell, P. (2003). Desensitization of β2-adrenoceptor-mediated responses by short-acting β2-adrenoceptor agonists in human lung mast cells. British Journal of Pharmacology, 138(3), 512–520.

Chorley, B., Li, Y., Fang, S., Park, J., & Adler, K. (2006). R-albuterol elicits antiinflammatory effects in human airway epithelial cells via iNOS. American Journal of Respiratory Cell and Molecular Biology, 34(1), 119–127.

Cockcroft, D., Davis, B., Swystun, V., & Marciniuk, D. (1999). Tolerance to the bronchoprotective effect of β2-agonists: Comparison of the enantiomers of salbutamol with racemic salbutamol and placebo. The Journal of Allergy and Clinical Immunology, 103(6), 1049–1053.

Cooper, P. R., & Panettieri, R. A. Jr. (2008). Steroids completely reverse albuterol-induced β(2)-adrenergic receptor tolerance in human small airways. The Journal of Allergy and Clinical Immunology, 122(4), 734–740.

Cooper, P., Kurten, R., Zhang, J., Nicholls, D., Dainty, I., & Panettieri, R. (2011). Formoterol and salmeterol induce a similar degree of β2-adrenoceptor tolerance in human small airways but via different mechanisms. British Journal of Pharmacology, 163(3), 521–532.

Costello, J. (1999). Prospects for improved therapy in chronic obstructive pulmonary disease by the use of levalbuterol. The Journal of Allergy and Clinical Immunology, 104(2Pt2), S61–68.

De Santi, C., Pietrabissa, A., Mosca, F., Rane, A., & Pacifici, G. M. (2002). Inhibition of phenol sulfotransferase (SULT1A1) by quercetin in human adult and foetal livers. Xenobiotica, 32(5), 363–368.

De Santi, C., Pietrabissa, A., Spisni, R., Mosca, F., & Pacifici, G. (2000). Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids. Xenobiotica, 30(9), 857–866.

Delmotte, Р., & Sanderson, M. J. (2008). Effects of albuterol isomers on the contraction and Ca2+ signaling of small airways in mouse lung slices. American Journal of Respiratory Cell and Molecular Biology, 38, 524–531.

Derom, E., Gayan-Ramirez, G., Gurrieri, G., de Bock, V., & Decramer, M. (1997). Broxaterol increases force output of fatigued canine diaphragm more than salbutamol. American Journal of Respiratory and Critical Care Medicine, 155(1), 181–185.

Duffy, S., Cruse, G., Lawley, W., & Bradding, P. (2005). β2-adrenoceptor regulation of the K+ channel iKCa1 in human mast cells. The FASEB Journal, 19(8), 1006–1008.

Dunn, R., Kolaja, K., & Klaassen, C. (1999). Effect of partial hepatectomy on the expression of seven rat sulphotransferase mRNAs. Xenobiotica, 29(6), 583–593.

Eaton, E., Walle, U., Wilson, H., Aberg, G., & Walle, T. (1996). Stereoselective sulphate conjugation of salbutamol by human lung and bronchial epithelial cells. British Journal of Clinical Pharmacology, 41(3), 201–206.

Esau, S. A. (1989). Hypoxic, hypercapnic acidosis decreases tension and increases fatigue in hamster diaphragm muscle in vitro. The American Review of Respiratory Disease, 139(6), 1410–1417.

Ferrada, M., Gordon, E., Jen, K., He, H., Lu, X., Barone, L., & Finn, P. W. (2008). (R)-albuterol decreases immune responses: Role of activated T cells. Respiratory Research, 9(1), 3.

Fried, K., Koch, P., & Wainer, I. (1998). Determination of the enantiomers of albuterol in human and canine plasma by enantioselective high-performance liquid chromatography on a teicoplanin-based chiral stationary phase. Chirality, 10(5), 484–491.

Frieri, M., & Capetandes, A. (2008). The effect of enantiomers of β-agonists on myofibroblast-derived vascular endothelial growth factor and other matrix components in the presence of dust-mite extract. Allergy and Asthma Proceedings, 29(2), 182–188.

Frohock, J., Wijkstrom-Frei, C., & Salathe, M. (2002). Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells. Journal of Applied Physiology, 92(6), 2396–2402.

Gashaw, I., Ellinghaus, P., Sommer, A., & Asadullah, K. (2012). What makes a good drug target? Drug Discovery Today, 17(Suppl.), S24–30.

Gaskell, H., Derry, S., Wiffen, P., & Moore, R. (2017). Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults. The Cochrane Database of Systematic Reviews (CD007355).

Günay, S., Sarıaydın, M., & Yılmaz, D. N. (2016). New bronchodilators and combinations in COPD treatment. Tuberkuloz Ve Toraks, 64(3), 240–245.

Gutierrez-Climente, R., Gomez-Caballero, A., Guerreiro, A., Garcia-Mutio, D., Unceta, N., Goicolea, M., & Barrio, R. (2017). Molecularly imprinted nanoparticles grafted to porous silica as chiral selectors in liquid chromatography. Journal of Chromatography A, 1508, 53–64.

Handley, D. (1999). The asthma-like pharmacology and toxicology of S-isomers of β agonists. The Journal of Allergy and Clinical Immunology, 104(2Pt2), S69–76.

Handley, D. A., Morley, J., & Vaickus, L. (1998). Levalbuterol hydrochloride. Expert opinion on investigational drugs, 7(12), 2027–2041.

Handley, D., McCullough, J., Crowther, S., & Morley, J. (1998). Sympathomimetic enantiomers and asthma. Chirality, 10(3), 262–272.

Hauck, R., Harth, M., Schulz, C., Präuer, H., Böhm, M., & Schömig, A. (1997). Effects of β2-agonist- and dexamethasone-treatment on relaxation and regulation of β-adrenoceptors in human bronchi and lung tissue. British Journal of Pharmacology, 121(8), 1523–1530.

Henderson, W., Banerjee, E., & Chi, E. (2005). Differential effects of S- and R-enantiomers of albuterol in a mouse asthma model. The Journal of Allergy and Clinical Immunology, 116(2), 332–340.

Herepath, M. L., & Broadley, K. J. (1992). Resistance of β2-adrenoceptor-mediated responses of lung strips to desensitization by long-term agonist exposure-comparison with atrial β1-adrenoceptor-mediated responses. European Journal of Pharmacology, 215(2–3), 209–219.

Honda, Z., Ishii, S., & Shimizu, T. (2002). Platelet-activating factor receptor. Journal of Biochemistry, 131(6), 773–779.

Ibe, B. O., Abdallah, M. F., & Raj, J. U. (2008). Mechanisms by which S-albuterol induces human bronchial smooth muscle cell proliferation. International Archives of Allergy and Immunology, 146(4), 321–333.

Ibe, B., Portugal, A., & Raj, J. (2006). Levalbuterol inhibits human airway smooth muscle cell proliferation: Therapeutic implications in the management of asthma. International Archives of Allergy and Immunology, 139(3), 225–236.

Ito, T., Fujimura, N., Omote, K., & Namiki, A. (2006). A selective β2-adrenergic agonist, terbutaline, improves sepsis-induced diaphragmatic dysfunction in the rat. Life Sciences, 79(9), 905–912.

Jacobson, G., Raidal, S., Robson, K., Narkowicz, C., Nichols, D., & Haydn, W. E. (2017). Bronchopulmonary pharmacokinetics of R-salbutamol and S-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses. British Journal of Clinical Pharmacology, 83(7), 1436–1445.

Jantikar, A., Brashier, B., Maganji, M., Raghupathy, A., Mahadik, P., Gokhale, P., & Salvi, S. (2007). Comparison of bronchodilator responses of levosalbutamol and salbutamol given via a pressurized metered dose inhaler: A randomized, double blind, single-dose, crossover study. Respiratory Medicine, 101(4), 845–849.

Javaheri, S., Smith, J., Thomas, J., Guilfoile, T., & Donovan, E. (1988). Albuterol has no effect on diaphragmatic fatigue in humans. The American Review of Respiratory Disease, 137(1), 197–201.

Keir, S., Page, C., & Spina, D. (2002). Bronchial hyperresponsiveness induced by chronic treatment with albuterol: Role of sensory nerves. The Journal of Allergy and Clinical Immunology, 110(3), 388–394.

Klaassen, C., Liu, L., & Dunn, R. (1998). Regulation of sulfotransferase mRNA expression in male and female rats of various ages. Chemico-Biological Interactions, 109, 299–313.

Ko, K., Kurogi, K., Davidson, G., Liu, M., Sakakibara, Y., Suiko, M., & Liu, M. (2012). Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases. Journal of Biochemistry, 152(3), 275–283.

Kubinyi, H. (2002). Chemical similarity and biological activities. Journal of the Brazilian Chemical Society, 13(6), 717–726.

Kuchay, M. S., & Mithal, A. (2017). Levosulpiride and serum prolactin levels. Indian Journal of Endocrinology and Metabolism, 21(2), 355.

Kurosawa, N., Morishima, S., Owada, E., & Ito, K. (1993). Comparison of bioavailability of salbutamol between oral and rectal administration in rabbits. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan, 113(4), 321–326.

Kurosawa, N., Owada, E., & Ito, K. (1993). Absorption and first-pass-effect of salbutamol after intraduodenal and intrarectal administration in rabbits. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan, 113(10), 698–704.

Lemoine, H., Overlack, C., Köhl, A., Worth, H., & Reinhardt, D. (1992). Formoterol, fenoterol, and salbutamol as partial agonists for relaxation of maximally contracted guinea pig tracheae: Comparison of relaxation with receptor binding. Lung, 170(3), 163–180.

Li, L., Cheng, B., Zhou, R., Cao, Z., Zeng, C., & Li, L. (2017). Preparation and evaluation of a novel N-benzyl-phenethylamino-β-cyclodextrin-bonded chiral stationary phase for HPLC. Talanta, 174, 179–191.

Li, L., Wu, C., Ma, Y., Zhou, S., Li, Z., & Sun, T. (2017). Effectively enhancing the enantioseparation ability of β-cyclodextrin derivatives by de novo design and molecular modeling. Analyst, 142(19), 3699–3706.

Liu, Y., Deng, M., Yu, J., Jiang, Z., & Guo, X. (2016). Capillary electrophoretic enantioseparation of basic drugs using a new single-isomer cyclodextrin derivative and theoretical study of the chiral recognition mechanism. Journal of Separation Science, 39(9), 1766–1775.

Marchetti, F., De, S. C., Vietri, M., Pietrabissa, A., Spisni, R., Mosca, F. (2001). Differential inhibition of human liver and duodenum sulphotransferase activities by quercetin, a flavonoid present in vegetables, fruit and wine. Xenobiotica, 31(12), 841–847.

Martin, L., Hobson, J., Page, J., & Harrison, C. (1971). Metabolic studies of salbutamol-3H: A new bronchodilator, in rat, rabbit, dog and man. European Journal of Pharmacology, 14(2), 183–199.

Matera, M., Calzetta, L., Rogliani, P., Bardaro, F., Page, C., & Cazzola, М. (2011). Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi. Pulmonary Pharmacology and Therapeutics, 24(2), 221–226.

Mazzoni, L., Naef, R., Chapman, I., & Morley, J. (1994). Hyperresponsiveness of the airways following exposure of guinea-pigs to racemic mixtures and distomers of β2-selective sympathomimetics. Pulmonary Pharmacology and Therapeutics, 7(6), 367–376.

McAuley, D., Frank, J., Fang, X., & Matthay, M. (2004). Clinically relevant concentrations of β2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury. Critical Care Medicine, 32(7), 1470–1476.

Milgrom, Н. (2006). Levosalbutamol in the treatment of asthma. Expert Opinion on Pharmacotherapy, 7(12), 1659–1668.

Mitra, S., Ugur, M., Ugur, O., Goodman, H., McCullough, J., & Yamaguchi, H. (1998). S-Albuterol increases intracellular free calcium by muscarinic receptor activation and a phospholipase C-dependent mechanism in airway smooth muscle. Molecular Pharmacology, 53(3), 347–354.

Mohammed, S. P., Taylor, C. V., Weyman-Jones, C. B., Mather, M. E., Vendy, K., Dougall, I. G., & Young, A. (2000). Duration of action of inhaled vs. intravenous β2-adrenoceptor agonists in an anaesthetized guinea-pig model. Pulmonary Pharmacology and Therapeutics, 13(6), 287–292.

Momose, T., Okubo, Y., Horie, S., Suzuki, J., Isobe, M., & Sekiguchi, M. (1998). Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression. International Archives of Allergy and Immunology, 117(2), 138–145.

Nakpheng, T., Songkarak, S., Suwandecha, T., Sritharadol, R., Chunhachaichana, C., & Srichana, T. (2017). Evidences for salbutamol metabolism by respiratory and liver cell lines. Drug Metabolism and Pharmacokinetics, 32(2), 127–134.

Nelson, H. S. (1999). Clinical experience with levalbuterol. The Journal of Allergy and Clinical Immunology, 104(2Pt2), S77–84.

Noguchi, S., Nishimura, T., Mukaida, S., Benet, L., Nakashima, E., & Tomi, M. (2017). Cellular uptake of levocetirizine by organic anion transporter 4. Journal of Pharmaceutical Sciences, 106(9), 2895–2898.

Nowak, R. (2003). Single-isomer levalbuterol: A review of the acute data. Current Allergy and Asthma Reports, 3(2), 172–178.

Pacifici, G. M. (2004). Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: A review of the literature. International Journal of Clinical Pharmacology and Therapeutics, 42(9), 488–495.

Page, C. P., & Morley, J. (1999). Contrasting properties of albuterol stereoisomers. The Journal of Allergy and Clinical Immunology, 104(2Pt2), S31–41.

Penn, R., Frielle, T., McCullough, J., Aberg, G., & Benovic, J. (1996). Comparison of R-, S-, and RS-albuterol interaction with human β1- and β2-adrenergic receptors. Clinical Reviews in Allergy and Immunology, 14(1), 37–45.

Píriz, H., Nin, N., Boggia, J., Angulo, M., & Hurtado, F. J. (2008). Salbutamol improves diaphragm force generation in experimental sepsis. Archivos de Bronconeumología (English Edition), 44(3), 135–139.

Reinero, C., Delgado, C., Spinka, C., DeClue, A., & Dhand, R. (2009). Enantiomer-specific effects of albuterol on airway inflammation in healthy and asthmatic cats. International Archives of Allergy and Immunology, 150(1), 43–50.

Roth, M., Nauck, M., Yousefi, S., Tamm, M., Blaser, K., Perruchoud, A. (1996). Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor. The Journal of Experimental Medicine, 184(1), 191–201.

Sabater, J., Lee, T., & Abraham, W. (2005). Comparative effects of salmeterol, albuterol, and ipratropium on normal and impaired mucociliary function in sheep. Chest, 128(5), 3743–3749.

Sardella, R., Ianni, F., Di Michele, A., Di Capua, A., Carotti, A., Anzini, M., & Natalini, B. (2017). Enantioresolution and stereochemical characterization of two chiral sulfoxides endowed with COX-2 inhibitory activity. Chirality, 29(9), 536–540.

Scola, A., Chong, L., Suvarna, S., Chess-Williams, R., & Peachell, P. (2004). Desensitisation of mast cell β2-adrenoceptor-mediated responses by salmeterol and formoterol. British Journal of Pharmacology, 141(1), 163–171.

Shen, Q., Wang, L., Zhou, H., Jiang, H., Yu, L., & Zeng, S. (2013). Stereoselective binding of chiral drugs to plasma proteins. Acta Pharmacologica Sinica, 34(8), 998–1006.

Sjöswärd, K. N., Josefsson, M., Ahlner, J., Andersson, R. G., & Schmekel, B. (2003). Metabolism of salbutamol differs between asthmatic patients and healthy volunteers. Basic and Clinical Pharmacology and Toxicology, 92(1), 27–32.

Soriano-Ursúa, M., Trujillo-Ferrara, J., Alvarez-Cedillo, J., & Correa-Basurto, J. (2010). Docking studies on a refined human β(2) adrenoceptor model yield theoretical affinity values in function with experimental values for R-ligands, but not for S-antagonists. Journal of Molecular Modeling, 16(3), 401–409.

Stank, А., Kokh, D., Fuller, J., & Wade, R. (2016). Protein binding pocket dynamics. Accounts of Chemical Research, 49(5), 809–815.

Suiko, M., Kurogi, K., Hashiguchi, T., Sakakibara, Y., & Liu, M. (2017). Updated perspectives on the cytosolic sulfotransferases (SULTs) and SULT-mediated sulfation. Bioscience, Biotechnology, and Biochemistry, 81(1), 63–72.

Theron, A., Steel, H., Tintinger, G., Feldman, C., & Anderson, R. (2013). Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting? Drug Design, Development and Therapy, 7, 1387–1398.

Tran, T., Friedman, J., Qunaibi, E., Baameur, F., Moore, R., & Clark, R. (2004). Characterization of agonist stimulation of cAMP-dependent protein kinase and G protein-coupled receptor kinase phosphorylation of the β2-adrenergic receptor using phosphoserine-specific antibodies. Molecular Pharmacology, 65(1), 196–206.

Uzuki, M., Yamakage, M., Fujimura, N., & Namiki, A. (2006). Preferable inotropic action of procaterol, a potent bronchodilator, on impaired diaphragmatic contractility in an intraabdominal septic model. Journal of Anesthesia, 20(2), 145–148.

Uzuki, M., Yamakage, M., Fujimura, N., & Namiki, A. (2007). Direct inotropic effect of the β-2 receptor agonist terbutaline on impaired diaphragmatic contractility in septic rats. Heart and Lung: The Journal of Acute and Critical Care, 36(2), 140–147.

Välitalo, P. A., Kemppainen, H., Kulo, A., Smits, A., Calsteren, K., Olkkola, K. T., & Allegaert, K. (2017). Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics. British Journal of Clinical Pharmacology, 83(9), 1966–1975.

Van der Heijden, H., Dekhuijzen, P., Folgering, H., & van Herwaarden, C. (1997). Inotropic effects of salbutamol on rat diaphragm contractility are potentiated by foreshortening. American Journal of Respiratory and Critical Care Medicine, 155(3), 1072–1079.

Vietri, M., Pietrabissa, A., Mosca, F., Rane, A., & Pacific, G. (2001). Human adult and foetal liver sulphotransferases: Inhibition by mefenamic acid and salicylic acid. Xenobiotica, 31(3), 153–161.

Vietri, M., Pietrabissa, A., Spisni, R., Mosca, F., & Pacifici, G. (2000). Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid. European Journal of Clinical Pharmacology, 56(5–6), 477–479.

Vietri, M., Vaglini, F., Pietrabissa, A., Spisni, R., Mosca, F., & Pacifici, G. (2002). Sulfation of R(-)-apomorphine in the human liver and duodenum, and its inhibition by mefenamic acid, salicylic acid and quercetin. Xenobiotica, 32(7), 587–594.

Volcheck, G., Kelkar, P., Bartemes, K., Gleich, G., & Kita, H. (2005). Effects of R- and S-isomers of β-adrenergic agonists on eosinophil response to interleukin-5. Clinical and Experimental Allergy, 35(10), 1341–1346.

Wang, X. S., & Lau, H. Y. (2006). β-adrenoceptor-mediated inhibition of mediator release from human peripheral blood-derived mast cells. Clinical and Experimental Pharmacology and Physiology, 33(8), 746–750.

Westerhof, F., Zuidhof, А., Kok, L., Meurs, Н., & Zaagsma, J. (2005). Effects of salbutamol and enantiomers on allergen-induced asthmatic reactions and airway hyperreactivity. European Respiratory Journal, 25, 864–872.

Xu, X., Zhou, J., Yang, Q., Fang, L., Xie, Q., & Shen, Y. (2006). An in vitro rat diaphragmatic fatigue model induced by combined hypoxic and hypercapnic acidosis and the effect of salmeterol. Pharmacological Research, 53(2), 171–176.

Yao, Y., Song, P., Wen, X., Deng, M., Wang, J., & Guo, X. (2017). Chiral separation of 12 pairs of enantiomers by capillary electrophoresis using heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin as the chiral selector and the elucidation of the chiral recognition mechanism by computational methods. Journal of Separation Science, 40(14), 2999–3007.

Zhang, Y., Wu, D., Wang-Iverson, D., & Tymiak, A. (2005). Enantioselective chromatography in drug discovery. Drug Discovery Today, 10(8), 571–577.

Zhou, T., Zeng, J., Liu, S., Zhao, T., Wu, J., Lai, W. (2015). Study on the determination and chiral inversion of R-salbutamol in human plasma and urine by liquid chromatography-tandem mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1002, 218–227.

How to Cite
Miroshnichenko, A. G., Bulgakova, Y. S., Perfiliev, V. Y., & Bazarnova, N. G. (2017). Levosalbutamol as alternative to drugs on the basis of racemic salbutamol: Review of the results of pre-clinical research. Regulatory Mechanisms in Biosystems, 8(4), 583–595. https://doi.org/10.15421/021790