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Clenbuterol Research

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2 years ago #1
Ziller33
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 Ziller33
Ziller33
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Clenbuterol focus: Research on Clen & Beta2- Adrenergic Compounds, Protocols
Author: Type-IIx

Research considerations

Clenbuterol is a drug legally used in human medicine in a select few countries as a bronchodilator at doses up to 40µg daily [18]. Primarily, it is used illicitly as a potent repartitioning agent to promote growth in cattle and sheep by increasing protein accretion and fat removal with little or no change in body weight, and by human athletes for this effect [8].

This work thus makes some extrapolation from animal research on clenbuterol as well as from human research on similar compounds (i.e., salbutamol/albuterol, terbutaline).

Pharmacokinetics

Clenbuterol is a β₂-adrenergic agonist similar in some structural respects to salbutamol (albuterol). Agonism of the β₂ receptor stimulates adenylyl cyclase activity which ultimately leads to downstream effects of smooth muscle relaxation in the bronchioles as a therapeutic target. Clenbuterol is a potent sympathomimetic.

Oral bioavailability of 70-80% and a long half-life of 25-39 hours [6].

Desensitization

Tachyphylaxis, or desensitization, is a feature of the β₂AR. This is likely because β₂AR activation and stimulation of downstream effects are a target for phosphorylation (50) and/or because it binds β-arrestin (51), an accessory protein involved in G protein-coupled receptor desensitization (52) [16].

Tolerability

High doses of clenbuterol have been used in the literature. The highest doses used are for patients with LVAD (left ventricular atrioventricular devices) and congestive heart failure. For this purpose, clenbuterol is used specifically for its effects on cardiac remodeling! It is important to note that cardiac remodeling should generally be avoided by healthy persons (though the remodeling from clen is ostensibly not maladaptive)! There was no change in LV mass with 80 µg daily for 3 months, [19].

Otherwise, an important research consideration is that tolerability cannot be assessed nor inferred from dosages administered in studies. Rather, tolerability must be assessed as an endpoint in the trial, in order to be able to make a claim regarding the drug's tolerability.

Here, this author presents some actual data on tolerability where it has been assessed as an end-point.

From a study on patients with heart failure. Here, the dosage started at 20µg twice daily and was titrated up to 40µg twice daily after a week [19]. Two of the nineteen (2/19) subjects dropped out of the 3 months-long study due to clenbuterol side effects:

Clenbuterol at 80µg/day was well tolerated [19].

Two clenbuterol subjects required discontinuation of study drug (asymptomatic slow ventricular tachycardia, severe muscle cramps without significant elevation increatine kinase [CK]) [19].

One further clenbuterol subject had a high rate of ventricular ectopy that disappeared without reduction in the clenbuterol dose [19].

One placebo subject had frequent non-sustained ventricular tachycardia. There were no implantable cardioverter-defibrillator discharges during the course of the study [19].

Six clenbuterol and 2 placebo subjects reported mild muscle cramps [19].

The CK value was elevated in 5 clenbuterol and 4 placebo subjects. The range of peak CK was 300 to 597 mg/dl in clenbuterol subjects and 305 to 408 mg/dl with placebo. Three clenbuterol subjects had cramps without elevation of CK, and CK was elevated in 1 clenbuterol subject who was asymptomatic. Of importance was that the CK level decreased despite continued drug administration (Figure 1B) [19].

Tremors were reported in 5 clenbuterol and 2 placebo subjects [19].

In a large, double-blind clinical trial (n=175 women with stress incontinence, 82 received 40µg clen daily for 2 weeks):

Side effects were noted in 13 clenbuterol-administered patients (15.9%), and the treatment was discontinued in 5 of these (due to tremors of the finger in 2

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