NIMODIPINE use in M.E. / CFS : A comprehensive guide. S. Parker (MBA, BSc) January 2014

[pattismith]

For those who want to try NIMODIPINE, (a L voltage gated calcium channel blocker, vasodilatator and neuroprotective drug), and who need a document to bring to their doctor.


https://www.actionforme.org.uk/assets/components/discuss/attachments/2/6193/nimodipine use in me, jan 2014.pdf

 

[S-VV]

I use Nimodipine. It gives a noticeable cognitive benefit.

I wonder how many more treatments like this are buried in the web...

 

[Mel9]

I have been using amlodipine for a month now and my POTS symptoms have started to improve.

 

[elfab]

I use Nimodipine. It gives a noticeable cognitive benefit.

I wonder how many more treatments like this are buried in the web...

Do you also have increased energy ?

 

[pattismith]

One pathway that could explain the positive effect of Nimodipine on ME/CFS is the nucleotide transporter inhibition.

"Among the dihydropyridines tested, nimodipine proved to be the most potent inhibitor of hENT-1, ..., whereas nifedipine, nicardipine, nitrendipine, and felodipine exhibited 100-fold less effective inhibitory activity. Nifedipine, nitrendipine, and nimodipine inhibited hENT-2 ....; however, nicardipine and felodipine had no significant effect on hENT-2"

One of the nucleotide transported is adenosine, which means that Nimodipine is an ADENOSINE REUPTAKE INHIBITOR, so it increases blood adenosine level and activation of adenosine receptors.

On the other hand, some L Calcium channel blockers have inhibition effect on some adenosine receptors, mainly A1 and A3 receptors.

"Pyridine derivatives, when bearing a 4-alkyl but not a 4-phenyl group, maintained affinity for adenosine receptors. These findings indicate that the dihydropyridines may provide leads for the development of novel, selective A3 adenosine antagonists."

This means that Nimodipine may enhance A2 receptors activity and decrease A1 and A3, which is exactely what we need, because A1 lower cAMP and A2 increases cAMP.

"All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors.
The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity.
The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity.
In addition, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity."
" Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory"

EDIT: about Mast cell degranulation for those that are concerned by this issue:


." In different animal models A1, A2b and A3 adenosine receptor subclasses have all been implicated in inducing bronchospasm. whilst occupation of the A2a receptor generally has no, or the opposite effect"

so this explains why Nimodipine might not having much bad effect on mast cells degranulation, as it may produce an indirect activation of A2 receptors, and inhibition of A1 and A3

 

[Dechi]

I’ve been using it for a few years. At first I was taking higher doses but this is very expensive and after a while I just went down to a small maintenance dose.

 

[pattismith]

@Gingergrrl

This is a 2019 study, it makes a link between beta 2 adrenergic receptor and L type VGCC

"The beta 2 adrenergic receptor (b2AR) has been identified as a potential mediator for this - a receptor that our lab has shown tightly regulates the activity of the L-type voltage-gated calcium channel 1.2 (Cav1.2).
Together these results support our hypothesis by showing that bA42 acts through b2AR to partially upregulate Cav1.2 activities in neurons and that such upregulation can be inhibited by blocking b2AR. Future work will exemplify this upregulation mechanism by examining its contributions to cytotoxicity and AMPAR expression."

"Gated Calcium Channel 1.2 through the Beta-2 Adrenergic Receptor"

 

[Gingergrrl]

@Gingergrrl This is a 2019 study, it makes a link between beta 2 adrenergic receptor and L type VGCC

I'm sorry I was so late to see your tag @pattismith. I am horrible at understanding scientific studies but is there a connection between the beta adrenergic autoantibodies and the L type VGCC or only between the receptor and the L type VGCC? As far as I know, there is no commercial test for the L type autoantibodies and only for the N type and P/Q type. What does this study mean (in very basic terms )?

 

[pattismith]

I'm sorry I was so late to see your tag @pattismith. I am horrible at understanding scientific studies but is there a connection between the beta adrenergic autoantibodies and the L type VGCC or only between the receptor and the L type VGCC? As far as I know, there is no commercial test for the L type autoantibodies and only for the N type and P/Q type. What does this study mean (in very basic terms )?

this makes a connection between POTS study that found antibodies activating the beta 2 adrenergic receptors, which means that L type VGCC are also activated in POTS, as a consequence of beta2 AR activation.
So this could explain at less partly why Nimodipine (L VGCC blocker) could have some effect for people with some kind of dysautonomia, especially when beta 2 AR are pathologically activated.

Not sure if I am clear!
Hip made some explanations about autoantibodies in POTS here

 

[Gingergrrl]

this makes a connection between POTS study that found antibodies activating the beta 2 adrenergic receptors, which means that L type VGCC are also activated in POTS

Do you know if there is a commercial test (outside of research studies) for autoantibodies of the L-type calcium channel (VGCC)? I have been trying to figure this out for several years b/c I have autoantibodies against the N-type but not against the P/Q type (on tests from Mayo & Quest). But I have not found any lab that tests the L-type and I am so curious b/c certain meds and anesthesias involve the L-type and I do not know if they would affect me without knowing if I have the autoantibodies.

 

[mitoMAN]

Very interesting. I have Beta 2 Receptor Autoantibodies and just stumbled across this thread.
Will give it a try!

From what I see this could be combined with low dose Propranolol to further block the Beta 2 AR Activation?

this makes a connection between POTS study that found antibodies activating the beta 2 adrenergic receptors, which means that L type VGCC are also activated in POTS, as a consequence of beta2 AR activation.
So this could explain at less partly why Nimodipine (L VGCC blocker) could have some effect for people with some kind of dysautonomia, especially when beta 2 AR are pathologically activated.

 

[mitoMAN]

@Mel9 @S-VV do you still use Nimodipine and do the benefits remain?

 

[S-VV]

Nope, like most direct interventions, the benefits fades with time

 

[Rufous McKinney]

For those who want to try NIMODIPINE, (a L voltage gated calcium channel blocker, vasodilatator and neuroprotective drug), and who need a document to bring to their doctor.

I wonder- why am I so late to even know that this exists? I should definately be trying this but apparently have not spent enough time yet here in PR to know it existed.

 

[mitoMAN]

May I ask if anyone had combined Nimodipine with Abilify?