Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders.

@article{Desaphy2003DifferentAO,
  title={Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders.},
  author={Jean-François Desaphy and Sabata Pierno and Annamaria De Luca and Paola Didonna and Diana Conte Camerino},
  journal={Molecular pharmacology},
  year={2003},
  volume={63 3},
  pages={
          659-70
        }
}
Activation of muscle beta(2)-adrenergic receptors successfully counteracted sarcolemma inexcitability in patients suffering from hyperkalemic periodic paralysis (HPP), a hereditary disease caused by mutations in the gene encoding the skeletal muscle sodium channel. Looking for potential modulation of these channels by beta(2)-adrenergic pathway using patch-clamp technique, we found that clenbuterol blocked sodium currents (I(Na)) in rat skeletal muscle fibers and in tsA201 cells transfected… 

Figures and Tables from this paper

Clenbuterol-sensitive delayed outward potassium currents in a cell model of spinal and bulbar muscular atrophy.
TLDR
It is demonstrated that the protection provided by clenbuterol restores the normal function through the modulation of KV2-type outward potassium currents, possibly contributing to the protective effect on motor neuron toxicity in SBMA.
Inhibition of voltage-gated sodium channels by sumatriptan bioisosteres
TLDR
This study evaluated whether sumatriptan and its congeners may inhibit heterologously expressed hNav1.7 sodium channels using the patch-clamp method and hypothesized that use-dependent sodium channel blockade contributes to the analgesic activity of (R)-31b and (S)-22b.
Molecular Insights into the Local Anesthetic Receptor within Voltage-Gated Sodium Channels Using Hydroxylated Analogs of Mexiletine
TLDR
It is confirmed that the presence of hydroxyl groups to the aryloxy moiety of mexiletine greatly reduced sodium channel block, and molecular insights into the intimate interaction of local anesthetics with their receptor are provided.
Molecular Dissection of Lubeluzole Use–Dependent Block of Voltage-Gated Sodium Channels Discloses New Therapeutic Potentials
TLDR
Compared with other known sodium channel blockers, lubeluzole adds a third pharmacophoric point through its benzothiazole moiety, which greatly enhances high-affinity binding and use-dependent block, and may help in the development of new sodium channel inhibitors to provide pharmacotherapy for membrane excitability disorders, such as myotonia, epilepsy, or chronic pain.
Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state‐dependent block
TLDR
Simulations according to the modulated receptor hypothesis mimic the voltage‐dependent block of WT and mutant channels by flecainide and mexiletine, and suggest similar blocking mechanisms for the two drugs.
Effects of Benzothiazolamines on Voltage-Gated Sodium Channels.
TLDR
Riluzole and lubeluzole displayed very potent antimyotonic activity in a rat model of myotonia, allowing the launch of a pilot study in myotonic patients, and patch-clamp experiments suggest that the binding sites of both drugs overlap the local anesthetic receptor within the ion-conducting pathway.
Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines
TLDR
The results show that different β-blockers have differential effects on whole-cell currents and free Ca2+i release and that propranolol activates store-operated Ca2-i release via a mechanism that involves calcium-induced calcium release and putative downstream transducers such as IP3.
...
...

References

SHOWING 1-10 OF 46 REFERENCES
Gating of myotonic Na channel mutants defines the response to mexiletine and a potent derivative
TLDR
These results explain the basis of the apparent difference in block of mutant sodium channels by mexiletine and Me7, opening the way to a more rationale drug use and to design more potent drugs able to correct specifically the biophysical defect of the mutation in individual myotonic patients.
Effects of propranolol and a number of its analogues on sodium channels.
Actions of sympathomimetic amines and their antagonists on skeletal muscle.
TLDR
It may be that, although mediated by different types of receptor, epinephrine exerts an effect on the coupling of excitation and transmitter release in nerve which is analogous to its action on excitation-contraction coupling in muscle, both effects involving changes in the levels of free calcium ions.
Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol
TLDR
The anticonvulsant effects of higher doses of clenbuterol against generalized tonic-clonic and complex partial seizures seem to be related to the inhibition of voltage-dependent sodium channels and not to the modulation of β-adrenoceptors.
Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.
TLDR
F1764 and Y1771 are common molecular determinants of state-dependent binding of diverse drugs including lidocaine, phenytoin, flecainide, and quinidine, suggesting that these drugs interact with a common receptor site.
Anabolic effects of clenbuterol on skeletal muscle are mediated by beta 2-adrenoceptor activation.
TLDR
The results indicate that the anabolic effects of clenbuterol are dependent on interaction with the beta 2-adrenoceptor, and a long duration of action appears to be required to induce the an metabolic effects ofbeta 2-agonists.
Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation.
TLDR
It is shown that sodium currents in rabbit cardiac myocytes are enhanced by isoproterenol (ISO), which suggests that ISO enhances rabbit cardiac INa through a dual (direct and indirect) G protein regulatory pathway.
Partial recovery of skeletal muscle sodium channel properties in aged rats chronically treated with growth hormone or the GH-secretagogue hexarelin.
TLDR
These results confirm the specific age-related changes in sodium channel behavior and show that treatment with either GH or hexarelin has partial restorative effects, which support the possible therapeutic value of the synthetic peptide in cases of GH deficiency, as in the elderly.
Blockade by cAMP of native sodium channels of adult rat skeletal muscle fibers.
TLDR
The results indicate that cAMP inhibits native skeletal muscle sodium channels by acting within the fiber, independently of PKA activation, according to the cell-attached patch-clamp technique.
Characterization of beta-adrenergic receptors of human skeletal muscle obtained by needle biopsy.
TLDR
Human skeletal muscle beta-adrenergic receptors were characterized by 125I-iodopindolol radioligand-binding studies of homogenates prepared from small muscle samples obtained by percutaneous needle biopsy from the gastrocnemius of six normal subjects to support pharmacological observations of beta- adrenergic receptor-mediated cellular responses in mammalian skeletal muscle.
...
...