Topic:Clenbuterol
Clenbuterol is a beta-2 adrenergic agonist commonly used in veterinary medicine to manage respiratory conditions in horses due to its bronchodilator properties. It facilitates breathing by relaxing the muscles in the airways, thereby improving airflow to the lungs. Clenbuterol is also known to have anabolic effects, which has led to its misuse in some contexts for enhancing muscle mass and performance in horses. The use of clenbuterol is regulated in competitive equestrian sports due to its potential impact on performance. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, therapeutic applications, regulatory considerations, and potential side effects of clenbuterol in equine practice.
Tissue distribution of clenbuterol in the horse. Plasma and tissue concentrations of clenbuterol (CLB) were determined following oral (p.o.) administration of 1.6 microg/kg twice daily (b.i.d.) for 2 weeks. Horses were administered the last dose on morning of day 15, killed at 0.25, 24, 48, and 72 h post-administration. At 0.25 h, the highest tissue concentrations of CLB were found in the liver (16.21 ng/g), lung (6.48 ng/g), left ventricle (4.99 ng/g), kidney (3.35 ng/g), bronchi (2.56 ng/g), right ventricle (2.08 ng/g), and eye fluids (1.09 ng/g) all of which were higher than that of plasma (1.10 ng/mL). The elimination half-lives (t(1/2k)...
Pharmacokinetics and disposition of clenbuterol in the horse. The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life (t(1/2k)) of 9.2 h, area under the time-concentration curve (AUC) of 12.4 ng.h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution (V(d)) was 1616.0 mL/kg and plasma clearance (Cl) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrati...
The beta-agonist clenbuterol in mane and tail hair of horses. The beta2-agonist clenbuterol is commonly administered for therapeutic purposes in the horse, but its use an an anabolic agent is illegal. Clenbuterol can be detected in blood and urine for a relatively short period after administration and detection in hair could enhance the analytical range and be used to determine the history of clenbuterol application. Objective: That detection in mane or tail hair is possible over an extended period. Methods: Four horses received 0.8 microg clenbuterol hydrochloride/kg bwt b.i.d. for 10 days. Four other horses were used as untreated controls. Blood, urine...
Therapeutic clenbuterol treatment does not alter Ca2+ sensitivity of permeabilized fast muscle fibres from exercise trained or untrained horses. Clenbuterol is a beta2-adrenoceptor agonist primarily used for treating bronchospasm and alleviating the symptoms of chronic obstructive pulmonary disease (COPD) in the horse. In other species (rats, mice, sheep, and cattle), chronic high doses of clenbuterol (typically in the milligram per kilogram body weight range) has been shown to cause a muscle directed protein anabolic response. Clenbuterol can also modify muscle fibre composition and therefore potentially affect muscle function. This has implications for the performance of exercising horses being treated with therapeutic doses of clenb...
The detection and biotransformation of guanabenz in horses: a preliminary report. Guanabenz (2,6-dichlorobenzylidene-amino-guanidine) is a centrally acting antihypertensive drug whose mechanism of action is via alpha2 adrenoceptors or, more likely, imidazoline receptors. Guanabenz is marketed as an antihypertensive agent in human medicine (Wytensin tablets, Wyeth Pharmaceuticals). Guanabenz has reportedly been administered to racing horses and is classified by the Association of Racing Commissioners International as a class 3 foreign substance. As such, its identification in a postrace sample may result in significant sanctions against the trainer of the horse. The present ...
Chronic clenbuterol administration alters myosin heavy chain composition in standardbred mares. The purpose of this study was to examine changes in myosin heavy chain (MHC) composition due to chronic clenbuterol administration with or without exercise in mares. Unfit Standardbred mares (aged 10+/-3 years) were divided into four groups: clenbuterol (2.4 micro/kg BW twice daily) plus exercise (3 days/week for 20 min at 50% VO(2max); CLENEX; n=6), clenbuterol only (CLEN; n=6), exercise only (EX; n=5), and control (CON; n=6). Muscle biopsies were obtained from gluteus medius muscle before and after the eight-week training/administration period. MHC composition was determined via SDS gel elec...
Effect of daily clenbuterol and exogenous melatonin treatment on body fat, serum leptin and the expression of seasonal anestrus in the mare. A small percentage of mature mares continue to exhibit estrous cyclicity during the non-breeding season which is of interest because of the importance of timing of the breeding season to the equine breeding industry. Previously, it was demonstrated that the continuation of estrous cycles was more likely to occur in mature than young mares. Additionally, an apparent association exists between elevated body fat and increased circulating concentrations of leptin, and the occurrence of estrous cycles during the non-breeding season. Two experiments were conducted to test the hypothesis that pharmac...
Clenbuterol diminishes aerobic performance in horses. The purpose of this 8-wk study was to examine the effect of therapeutic levels of clenbuterol on aerobic performance and hemodynamics associated with exercise. Methods: Twenty-three unfit Standardbred mares were divided into four experimental groups, clenbuterol (2.4 microg x kg(-1) body weight twice daily) plus exercise (20 min at 50% O2max; CLENEX; N = 6), clenbuterol only (CLEN; N = 6), exercise only (EX; N = 5), and control (CON; N = 6). All horses performed an incremental exercise test (GXT) to measure maximal oxygen consumption (O2max), blood lactate concentration, total plasma protein c...
Comparison of serum and urinary concentrations of clenbuterol with and without concomitant administration of furosemide in horses. Furosemide is frequently used to control or prevent exercise-induced pulmonary hemorrhage in performance horses. The bronchodilating agent clenbuterol is also commonly used as a treatment for inflammatory airway disease in performance horses. Use of both medications is regulated by many racing authorities. The effects of concomitant administration of furosemide and clenbuterol on the pharmacokinetics of clenbuterol have not been well characterized. A study was designed to evaluate the influence of furosemide on serum and urine concentrations of clenbuterol after oral administration of clenbute...
Detection of inhaled clenbuterol in horse urine by GC/MS2. Clenbuterol, a beta-adrenergic agonist, is used in the treatment of recurrent airway obstruction in horses. It is prohibited by horse racing authorities, because of its stimulating and growth-promoting properties. However, information on detection times of clenbuterol after administration by nebulization is lacking. In this study, a fast, sensitive quantitative GC-MS(2) method for the detection of clenbuterol in urine was developed. Alkaline liquid-liquid extraction was followed by derivatization to a cyclic methyl boronate derivative and analysis on a Finnigan MAT GCQ instrument. Method valid...
Regulation of equine lymphocyte beta-adrenoceptors under the influence of clenbuterol and dexamethasone. In 12 healthy horses, the effects of the beta2-agonist clenbuterol and the glucocorticoid dexamethasone on the lymphocyte beta2-adrenoceptor density and affinity (determined by (-)-[125I]-iodocyanopindolol binding) as well as its responsiveness (assessed by lymphocyte cyclic AMP [cAMP] responses to 10 micromol/l (-)-isoprenaline) were studied. Clenbuterol treatment, 2 x 0.8 microg/kg/day i.v. for 12 days, decreased significantly ICYP binding sites by approximately 30-40%; concomitantly, lymphocyte cAMP response to (-)-isoprenaline was reduced. After withdrawal of clenbuterol, beta2-adrenocepto...
Quantification of clenbuterol in equine plasma, urine and tissue by liquid chromatography coupled on-line with quadrupole time-of-flight mass spectrometry. Clenbuterol (CBL) is a potent beta(2)-adrenoceptor agonist used for the management of respiratory disorders in the horse. The detection and quantification of CBL can pose a problem due to its potency, the relatively low dose administered to the horse, its slow clearance and low plasma concentrations. Thus, a sensitive method for the quantification and confirmation of CBL in racehorses is required to study its distribution and elimination. A sensitive and fast method was developed for quantification and confirmation of the presence of CBL in equine plasma, urine and tissue samples. The method i...
[Influencing respiratory gas analytical lung function parameters by intravenous injection of clenbuterol in horses with chronic lung diseases]. In a placebo-controlled drug study data were collected about flow, volume and expiratory CO2-concentration in 13 horses with chronic obstructive pulmonary disease before and until 2.5 h after intravenous injection of clenbuterol. An ultrasonic flow measuring unit and an infrared-CO2-analyser (Spiroson Scientific) were used. functional deadspace and expiratory mixed volume were calculated. In addition the effect on the partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) in arterial blood was tested and the alveolo-arterial oxygen difference (AaDO2) determined. The volume of the functio...
The effects of cAMP modulation upon the adhesion and respiratory burst activity of immune complex-stimulated equine neutrophils. Toxic products such as reactive oxygen intermediates released by activated polymorphonuclear neutrophil (PMN) have an important role in the pathophysiology of diseases associated with the deposition of immune complexes (IC) in tissues. IC-induced activation of PMN requires adhesion mediated by integrin adhesion receptors. Of the integrins expressed on PMN, the beta(2) family has been found to be of particular importance for activation of PMN by IC. beta(2) Integrin ligand binding must be activated to enable adhesion to IC. Both activating and inhibitory signals regulate beta(2) integrin ligand...
Chronic clenbuterol administration negatively alters cardiac function. Chronic administration of pharmacological levels of beta2-agonists have been shown to have toxic effects on the heart; however, no data exist on cardiac function after chronic clenbuterol administration. The purpose of this study was to examine the effect of therapeutic levels of clenbuterol on cardiac performance. Methods: Twenty unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 microg.kg(-1) twice daily 5 d.wk(-1)) plus exercise (20 min at 50% .VO(2max)) (CLENEX; N = 6), clenbuterol (CLEN; N = 6), exercise (EX; N = 4), and control (CON; N = 4). M-mode and ...
Chronic administration of therapeutic levels of clenbuterol acts as a repartitioning agent. The purpose of this study was to examine the effect of therapeutic levels of clenbuterol, with and without exercise training, on body composition. Twenty-three unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 microg/kg body wt twice daily) plus exercise (ClenEx; 20 min at 50% maximal oxygen consumption 3 days/wk; n = 6), clenbuterol only (Clen; n = 6), exercise only (Ex; n = 5), and control (Con; n = 6). Rump fat thickness was measured at 2-wk intervals by using B-mode ultrasound, and percent body fat (%fat) was calculated by using previously published meth...
Clenbuterol in the horse: confirmation and quantitation of serum clenbuterol by LC-MS-MS after oral and intratracheal administration. Clenbuterol is a beta2 agonist/antagonist bronchodilator, and its identification in post-race samples may lead to sanctions. The objective of this study was to develop a specific and highly sensitive serum quantitation method for clenbuterol that would allow effective regulatory control of this agent in horses. Therefore, clenbuterol-d9 was synthesized for use as an internal standard, an automated solid-phase extraction method was developed, and both were used in conjunction with a multiple reaction monitoring liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to allow unequivoca...
Clenbuterol in the horse: urinary concentrations determined by ELISA and GC/MS after clinical doses. Clenbuterol is a beta2 agonist/antagonist bronchodilator marketed as Ventipulmin and is the only member of this group of drugs approved by the US Food and Drug Administration (FDA) for use in horses. Clenbuterol is a class 3 drug in the Association of Racing Commissioners International (ARCI) classification system; therefore, its identification in postrace samples may lead to sanctions. Recently, the sensitivity of postrace testing for clenbuterol has been substantially increased. The objective of this study was to determine the 'detection times' for clenbuterol after administration of an oral...
Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise-induced pulmonary capillary hypertension in Thoroughbred horses. The stimulation of pulmonary beta2-adrenergic receptors causes a decrease in vascular resistance. Thus, the present study was carried out to examine whether concomitant administration of clenbuterol-a beta2-adrenergic receptor agonist, to horses premedicated with furosemide would attenuate the exercise-induced pulmonary capillary hypertension to a greater extent than furosemide alone, and in turn, affect the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control...
Intratracheal clenbuterol in the horse: its pharmacological efficacy and analytical detection. Clenbuterol, a beta2 agonist/antagonist, is the only bronchodilator approved by the US Food and Drug Administration for use in horses. The Association of Racing Commissioners International classifies clenbuterol as a class 3 agent, and, as such, its identification in post-race samples may lead to sanctions. Anecdotal reports suggest that clenbuterol may have been administered by intratracheal (IT) injection to obtain beneficial effects and avoid post-race detection. The objectives of this study were (1) to measure the pharmacological efficacy of IT dose of clenbuterol and (2) to determine the ...
Clenbuterol administration does not attenuate the exercise-induced pulmonary arterial, capillary or venous hypertension in strenuously exercising Thoroughbred horses. The present study was carried out to ascertain whether beta2-adrenergic receptor stimulation with clenbuterol would attenuate the pulmonary arterial, capillary and venous hypertension in horses performing high-intensity exercise and, in turn, modify the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Experiments were carried out on 6 healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications) and the clenbuterol (0.8 pg/kg bwt, i.v.) treatments. The sequence of these treatments was randomised for every horse, and 7 days were allowe...
Uterine contractility is necessary for the clearance of intrauterine fluid but not bacteria after bacterial infusion in the mare. Bacteria were infused into the uteri of 5 estrous mares resistant to persistent mating-induced endometritis, first during a control cycle, and then during treatment with clenbuterol, a beta 2 agonist. Uterine cellular response was evaluated 48 h later by transrectal ultrasonography, followed by uterine lavage. During clenbuterol treatment all mares accumulated intrauterine fluid, whereas in the control cycle none of the mares retained fluid. There was no significant difference between the 2 cycles in the cloudiness of the lavage fluid, number of cells per milliliter, percentage of neutrophils ...
Effect of oxytocin, prostaglandin F2 alpha, and clenbuterol on uterine dynamics in mares. The effects of oxytocin, prostaglandin F2 alpha (PGF2 alpha), and clenbuterol on uterine contractility and tone during anestrus and diestrus, and during mobility and postfixation of the embryonic vesicle were studied in 51 pony mares. Contractility was assessed by scoring real-time ultrasound images, and tone was assessed by transrectal digital compression. Scoring was done by an operator who had no knowledge of treatment assignments. In anovulatory mares primed with progesterone for 16 d, oxytocin did not significantly alter contractility but did stimulate an increase in tone, whereas clenbut...
Investigations on the ability of clenbuterol hydrochloride to reduce clinical signs and inflammation associated with equine influenza A infection. Twenty-four Quarter Horse and Quarter Horse-cross yearlings were experimentally infected with influenza A virus (Influenza A/equine/Saskatoon/90 [H3N8]) by nebulisation. In a double blind controlled trial the horses were randomly assigned to 3 groups of 8 animals. Group 1 received a placebo, (carrier syrup), Group 2 the labelled dose and Group 3 twice the labelled dose of clenbuterol hydrochloride. All treatments were given per os b.i.d. for 10 days and started on the day of infection. The horses were monitored for clinical signs of influenza infection for 14 days. Bronchoalveolar lavages were...
The cardiopulmonary effects of clenbuterol when administered to dorsally recumbent halothane-anaesthetised ponies–failure to increase arterial oxygenation. Clenbuterol (0.8 microg kg(-1) intravenously) was investigated in ponies (small horses) anaesthetised with acepromazine, detomidine and thiopentone, then halothane in oxygen alone (hyperoxic group) or with nitrous oxide (hypoxic group). Following instrumentation, ponies were placed in dorsal recumbency for 60 minutes, clenbuterol (both groups) or a saline control (hyperoxic group) given, and cardiopulmonary parameters monitored for a further 60 minutes. In the hyperoxic group, clenbuterol administration resulted in a transitory (<five minutes) 15 per cent fall in arterial blood pressure and...
A comparison between clenbuterol, salbutamol and terbutaline in relation to receptor binding and in vitro relaxation of equine tracheal muscle. Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the be...
Illegal use of beta-adrenergic agonists: European Community. The use of veterinary medicinal products within the European Community is governed by a series of directives and regulations that describe the requirements for safety, quality, and efficacy of these products. Veterinary therapeutic use of beta-agonists has only been approved in the case of clenbuterol for bronchodilatation in horses and calves and for tocolysis in cows. No beta-agonists have been permitted in the European Community for growth-promoting purposes in farm animals. Surveillance for the presence of residues of veterinary agents in food-producing animals and meat is regulated by the...
Relaxation of equine tracheal muscle in vitro by different adrenoceptor drugs. Strips of tracheal smooth muscle from 12 horses were contracted by carbachol in tissue baths under isometric conditions. This contraction (approximately 50% of maximum: EC50) was relaxed completely with adrenoceptor drugs. The only exception was clenbuterol, where the degree of relaxation was approximately 90%. In all horses the EC50-value for isoprenaline (mean 1.6 x 10(-8) M) was less than that for adrenaline (mean 9.6 x 10(-8) M) and noradrenaline (mean 1.8 x 10(-6) M). The potency ratio was 1 < 6 < 110 which indicates that the beta 2-subtype dominates among the beta-adrenoceptors of ...
Obstructive pulmonary disease in 18 horses at summer pasture. The clinical features of 18 cases of summer pasture associated obstructive pulmonary disease were reviewed. The horses had signs of obstructive pulmonary disease (expiratory dyspnoea, wheezing and crackling lung sounds and coughing) during the spring, summer or autumn while they were kept permanently at grass with no access to hay or straw, for at least two consecutive years. In nine cases there was a seasonal incidence with the disease occurring during April and May. Eleven of the horses were affected by bouts of severe dyspnoea. Eleven of the horses also suffered from chronic obstructive pul...