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Will 5-hydroxybenzothiazolone replace clenbuterol?

Will 5-hydroxybenzothiazolone replace clenbuterol?
Researchers at Novartis may have found a replacement for the time-honored beta-2-adrenoreceptor agonist clenbuterol. They will report this soon in the Journal of Pharmacology and Experimental Therapeutics. The researchers conducted animal studies with 5-hydroxybenzothiazolone [5-HOB], which show that the new drug has as much anabolic effect as formoterol but has far less cardiovascular side effects.

Beta-2 Adrenoreceptor Agonists
When natural in muscle cell naturel pep hormones such as adrenalin interact with the beta-2 adrenoreceptor, the cells will consume more energy and will slow down the decay of muscle proteins.

Therefore, pharmacological agents that stimulate the beta-2 adrenoreceptor are popular in fitness and bodybuilding. They are body-recompositioning drugs: they reduce fat mass but protect lean body mass.

Known beta-2 adrenoreceptor agonists are clenbuterol and formoterol.

Will 5-hydroxybenzothiazolone replace clenbuterol?

Treatment with beta-2 adrenoreceptor agonists is associated with cardiovascular side effects. The drugs can accelerate heart rate and raise blood pressure in the short term, and in the long term induce enlargement of the heart, and make the heart function less efficient. This may ultimately lead to heart failure.

In experiments with rats, 5-hydroxybenzothiazolone increased muscle mass. However, the dose required for this was higher than the dose required by beta-2 adrenoreceptor agonist formoterol to achieve muscle growth. But at this effective dose, 5-hydroxybenzothiazolone slightly increased the heart muscle, while formoterol caused a major heart enlargement.

Will 5-hydroxybenzothiazolone replace clenbuterol?

If anabolic agents such as testosteron, growth hormone or clenbuterol cause heart enlargement, this is usually negative. The enlargement makes that the heart can no longer pump blood through the body as it should. The heart's ejection fraction decreases.

And that also happened in rats given formoterol, the researchers discovered [bottom right]. However, this effect was not observed in rats receiving 5-hydroxybenzothiazolone.

Will 5-hydroxybenzothiazolone replace clenbuterol?

Another cardiovascular side effect of beta2-adrenoreceptor agonists is that they accelerate heart rate. This occurred to a lesser extent with 5-hydroxy-benzothiazolone than with formoterol [top left].

"The preclinical data reported in this study show that 5-hydroxy-benzothiazolone is a potent, selective beta-2-adrenoreceptor-agonist that is effective in promoting skeletal muscle growth", the researchers summarize their findings. "Furthermore, 5-hydroxybenzothiazolone displays tissue selectivity and reduced cardiovascular effects, when compared to the well-described representative beta-2-adrenoreceptor-agonist formoterol in preclinical studies."

"Hence, these data suggest that 5-hydroxybenzothiazolone may provide a new valuable treatment option for muscle atrophy conditions. Clinical studies will determine whether 5-hydroxybenzothiazolone has the potential for reduced cardiac side effects at therapeutic doses in humans compared with other conventional beta-2-adrenoreceptor-agonists, such as formoterol."

J Pharmacol Exp Ther. 2019 Feb 28. pii: jpet.118.255307. doi: 10.1124/jpet.118.255307. [Epub ahead of print].

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Beta-2 Agonists

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