This is part of a Darkham article over on Meso - What I would like to know is has anyone had any good experiences with using Dantrolene or any other calcium channel blocker? Also, what about the use of grapefruit seed extract or juice to enhace its effects and keep it in the bloodstream longer?
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How does muscle breakdown occur?
The most up-to-date theory concerning muscle breakdown involves two distinct steps. First, calcium-dependent proteases called calpains are upregulated by the calcium leaks induced by training. Each of our muscle cells hold on calcium in small pockets called sarcoplasmic reticulum. It is the rapid entry and exit of calcium from the sarcoplasmic reticulum which induces muscle contractions. Repeated contractions induce an impairment of this highly regulated calcium movement. Calcium accumulates inside the cell rather than in its sarcoplasmic reticulum reserve. The first consequence of this loss of homeostasis is the reduction of strength experienced as sets accumulate. The second long term consequence is the upregulation of the activity of calpain. Calpain in turn cuts out large chunks of myofibrils that are called easily releasable myofilaments. This is for the first act.

Second act: Those large pieces of muscle cells will then be attacked by another proteolytic mechanism called the ATP-dependent ubiquitin-proteasome pathway. Ubiquitin is only a marker which detects abnormal, denatured or damaged muscle proteins such as the easily releasable filaments. Then, the proteasome is attracted by these marked proteins because of their association with ubiquitin. Once attacked by the proteasome, a damaged protein is digested into single amino acids ready to be recycled as raw materials for muscle rebuilding or more likely as waste products such as urea. Needless to say, an intense workout rapidly increases the activities of both ubiquitin and the proteasomes.

I cannot stress enough the necessity of the large cuts to the myofibers for the ubiquitin and proteasome to act. If we can reduce the actions of the calpains, we can prevent the proteasome from acting. If the cleaving of muscle fiber doesn't take place, myofibers will be very resistant to the catabolic actions of the proteasome. On the other hand, a small break up of the contractile apparatus will markedly increase the likelihood of degradation by the proteasome. We should nonetheless also attempt to tame the activity of the proteasome. In this way we have two possible ways of acting to prevent catabolism. We'll combine them for maximum effect.

Dantrolene: The weapon against calpains.
We should first attempt to impair the normal functioning of muscle calpains. As calpains are activated by excessive calcium leaks, let's limit this leakage. Dantrolene is an oral drug which belongs to a class of medication called calcium channel blockers [1]. Dantrolene is the most muscle specific member of this class. This is why it is so popular among athletes. It is commonly used as a muscle relaxant. As intracellular calcium release is responsible for muscle contractions, inhibition of this release induces a relaxation of the muscles. This reduces the muscle's need for ATP, which allows a faster recovery of the training-induced diminution of the ATP "stores." By inhibiting the calcium release from the sarcoplasmic reticulum, Dantrolene will impair the normal activation of the calpains by training.

Dantrolene has two major flaws. First, it acts on every muscle and not only specifically on the trained muscles as we would wish for optimal effects. Second, as a muscle relaxant, it will reduce muscle strength if you are not extra careful about the intake timing and dosage. What you want is for Dantrolene to produce its magic right after but not during the workout. If your training lasts less than one hour, you can take Dantrolene before your workout. This way, the drug will kick in at the right time. If you train for more than an hour, it is best to take Drantrolene in the middle of your workout. Start with the 25 mg tablets and build up SLOWLY to the 200 to 300 mg per day. It is ideal if you work out at night as Dantrolene will help you to sleep (it is a relaxant). If you have to drive or to perform something which requires attention while you are supposed to be under the influence of this drug, please do not take it. However most people work out in the evening, so it should not be a problem. If you have to drive home after your workout, take Drantrolene right after your workout so that it kicks in while you are home ready to go to bed.