The beta(2)adrenergic receptor appears to be able to get desensitized, and can be desensitized by any agonist (including ephedrine). However, it also appears to have a fast resensitization rate once the agonist is out of the system. This may be secondary to the normally 'pulse'-like actions of adrenaline requiring rapid resensitization.
Due to this rapid resensitization of the receptor ephedrine acts on, it is unlikely that one needs to cycle ephedrine
A recent study submitted to the Public Library of Science journal (PLoS) tested a novel method to assess beta-adrengergic desensitization (Resonant waveguide grating (RWG) biosensor) that can work in live cells non-invasively and can gather much of the same results as conventional models.
Epinephrine agonism (the standard beta-adrenergic agonist) was able to cause some desensitization of beta(2)adrenergic receptors when constantly 'pulsed' in the medium for 5 minutes, although short acute bursts showed no effect on desensitization. The mechanism by which beta(2)adrenergic desensitization occurred was via receptor internalization (receptors hide from the surface of the cell and cannot be activated by the ligand). This is evident in immunostaining.
In removing a 1min pulse of ephedrine, resensitization of the receptor appears to occur within twenty minutes as evidenced by a greater cumulative post-receptor effect (upward trend of activation, rather than a static response). Specifically, Figure A. Similar effects were seen when the drugs with longer half-lives were interrupted with inhibitors of desensitization.
One study that tested in vitro desensitization of various beta(2)adrenergic agonists found ephedrine was the least effective at inducing desensitization when 90% of the receptor was occupied. The rate of desensitization was positively correlated with potency of activation.
The relatively rapid (within minutes) resensitization of the beta(2)adrenergic receptor has also been replicated.
Studies on long-lasting asthma medication (which also act via beta(2)adrenergic desensitization) have noted less efficacy and predictability with prolonged exposure. However, this is related to compound half-life rather than period of usage (as well as not being in fat cells).
One study with an admittedly low sample size of 5 noted that, with chronic usage of ephedrine at 20mg three times daily that acute ephedrine boluses were more effective at increasing the metabolic rate by attenuating the decline over 240 minutes. This suggests a sensitization effect, possibly related to higher serum adrenaline levels after 12 weeks supplementation.
Although Ephedrine may not need to be cycled to keep sensitivity, Caffeine is still subject to desensitization. It may be worth cycling the C fragment of the ECA stack, although the E does not need to be.
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