General description

Clenbuterol hydrochloride is a white or almost white crystalline powder. Odorless, slightly bitter taste. It is soluble in water or ethanol, slightly soluble in chloroform or acetone, and insoluble in ether. The chemical structure of clenbuterol hydrochloride is similar to that of epinephrine drugs. As a 2-receptor agonist, Clenbuterol hydrochloride has a high selective excitatory effect on the 2-receptor of bronchus, uterus and vascular smooth muscle, and can effectively relieve bronchospasm.

Fig. 1 The structure of Clenbuterol hydrochloride.

Enantiomer resolution

Resolution of clenbuterol hydrochloride enantiomers and propranolol hydrochloride enantiomers was achieved by thin-layer chromatography using methyl-beta-cyclodextrin impregnated silica gel GF254 plates. The effects of stereoselective auxiliary (acetonitrile/different alcohols) were studied. Resolution of clenbuterol hydrochloride enantiomers could be realized by alcohols such as ethanol, n-butanol, 2-butanol or tert-butanol together with acetonitrile, and propranolol hydrochloride enantiomers could only be resoluted by ethanol or n-butanol together with acetonitrile. The optical conditions of simultaneous resolution were obtained as follows: 15.00g silica gel GF254 plates impregnated with 1.00g methyl-beta-cyclodextrin, acetonitrile/n-butanol (VN = 90:10) mixed solvent as spreading solvent, being resolved under ambient temperature. Under these conditions, R-F value of resolution of clenbuterol hydrochloride enantiomers is 3.47, R-F value of resolution of propranolol hydrochloride enantiomers is 3.35. The two couples of enantiomers were all achieved base line separation [1].

Bioactivity

As a decongestant and bronchodilator

Clenbuterol hydrochloride is an active pharmaceutical ingredient usually prescribed for treatment of respiratory diseases due to its activity as a decongestant and bronchodilator. It has also been used as a performance-enhancing drug. In the PDF-4/Organics 2012 database there are six entries related to this compound: three for its hydrochloride phase calculated using single-crystal data, two for a McOH and a DMSO solvate of two Cu-clenbuterol complexes, and one experimental unindexed pattern. In this contribution the powder diffraction pattern and the crystal structure, determined using single crystal X-ray diffraction techniques of clenbuterol hemihydrate, C12H18Cl2N2O center dot 0.5H(2)O, an unreported phase, are presented [2].

The interaction of clenbuterol hydrochloride with bovine hemoglobin

The interaction of clenbuterol hydrochloride (CL) to bovine hemoglobin (BHb) under physiological conditions was investigated by using UV-vis absorption, fluorescence, circular dichroism (CD) and molecular modeling. The fluorescence intensity of BHb decreased regularly with the gradual increasing concentration of CL. It is observed that there was a prominent interaction between CL and BHb. The fluorescence data revealed that the fluorescence quenching is a static process, and the thermodynamic parameters were calculated according to the Van't Hoff equation. The alternations of protein secondary structure in the presence of CL were determined by the evidence of CD. Molecular modeling study that corroborate our experimental results revealed that the binding mode of CL-BHb complex could be attributed to the hydrophobic interaction and hydrogen bonding, but electronic interaction cannot be excluded [3].

Clinical studies

The clinical effectiveness and safety of terodiline hydrochloride and clenbuterol hydrochloride were studied on 51 patients with neurogenic bladder, stress incontinence, unstable bladder and others, the chief complaints of which were urinary frequency or urinary incontinence. Overall improvement was graded as marked in 6 patients (11.8%), moderate in 20 patients (39.2%), slight in 11 patients (21.6%), unchanged in 13 patients (25.5%) and aggravated in one. The patients impression was "good" or better in 56.9%. There were a total of 13 cases (25.5%) of adverse reactions, namely, 7 cases of finger tremor, 3 cases of dry mouth and others. These reactions disappeared rapidly after the discontinuance of drug administration. The clinical efficacy in the treatment of subjective symptoms was 71.4% for urinary incontinence, 56.4% for diurnal pollakisuria. The examination of lower urethral functions demonstrated a significant (p less than 0.01) increase in bladder capacity at first desire and maximum desire to void. However, we found no significant increase in urethral clossure pressure. The findings of this study suggest that terodiline hydrochloride and clenbuterol hydrochloride are very useful for the treatment of urinary frequency and incontinence [4].

References

[1] Yu J G, Huang D S. Simultaneous resolution of clenbuterol hydrochloride enantiomers and propranolol hydrochloride enantiomers using thin-layer chromatography[C]//Advanced Materials Research. Trans Tech Publications Ltd, 2011, 236: 1546-1548.

[2] Toro R, Bruno-Colmenárez J, de Delgado G D, et al. Structural characterization of a new form of clenbuterol, a well-known decongestant and bronchodilator also used as a performance-enhancing drug[J]. Powder Diffraction, 2013, 28(2): 63-67.

[3] Wu Y, Mao H, Zhao B, et al. The interaction of clenbuterol hydrochloride with bovine hemoglobin using spectroscopic techniques and molecular modeling methods[J]. Spectroscopy, 2009, 23(5-6): 271-279.

[4] Katsumi T, Murayama K, Tajika E, et al. Clinical studies of terodiline hydrochloride and clenbuterol hydrochloride for urinary frequency and incontinence[J]. Hinyokika kiyo. Acta Urologica Japonica, 1991, 37(11): 1575-1580.