Just came across an article on homocysteine - I was somewhat aware of its role in heart disease, but this also talks about its role in hitting the NMDA receptors, which trigger the calcium channels to dump.... that could be relevant to clusters.

NMDA receptors have been discussed in terms of cluster headaches before - less studied than serotonin, but there is evidence they are involved.  Glutamate (including MSG) is one thing that makes the NMDA receptors very active. 

Blocking the calcium channels, of course, is how verapamil works.

High levels of homocysteine are usually linked to diet, especially low levels of methyl donors (folate and vitamin B-12).  Choline is a methyl donor that is know to be very low in clusterheads - it could be low in CH from some specific metabolic glitch, but it could low due to a general deficiency in methyl donors. Other methyl donors related to choline include trimethylglycine and dimethyl glycine.




Quote:

Biochemistry (Mosc). 2009 Jun;74(6):589-98.Links     Molecular mechanisms of homocysteine toxicity.     Boldyrev AA.     Biological Faculty, Lomonosov Moscow State University     Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny.

Carnosine is a relatively cheap compound composed of two amino acids. Not sure that it is a methyl donor per se, but it seems to reduce the ability of NMDA neurons to trigger a calcium dump. It has a good safety profile, but I would not mix it with other calcium channel blockers since there might be an additive or multiplicative increase in the effects of verapamil.

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Quote:

Neuroscience. 1999;90(4):1371-6.     Trigeminovascular nociceptive transmission involves N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptors.     Storer RJ, Goadsby PJ.     Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.     Interest in the fundamental mechanisms underlying headache, particularly the pathophysiology of migraine and cluster headache, has lead to the study of the physiology and pharmacology of the trigeminovascular system and its central ramifications. Cats were anaesthetized (60 mg/kg alpha-chloralose, i.p., along with halothane for all surgical procedures) and prepared for physiological monitoring. The animals were placed in a stereotaxic frame and ventilated. A midline craniotomy and C2 laminectomy were performed for access to the superior sagittal sinus and C2 dorsal horn, respectively. The sinus was isolated from the underlying cortex and stimulated electrically after the animals had been paralysed with gallamine (6 mg/kg, i.v.). Units linked to stimulation were recorded with a tungsten-in-glass microelectrode placed in the most caudal part of the trigeminal nucleus, the trigeminocervical complex. Signals from the neurons were amplified, filtered and passed to a microcomputer, where post-stimulus histograms were constructed on-line to analyse the responses to stimulation. Units responded to sagittal sinus stimulation with a typical latency of 8-10 ms. All units studied had a probability of firing of 0.6 or greater. Intravenous injection of the non-competitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (4 mg/kg, i.v.), resulted in a substantial and prolonged blockade of firing of units in the trigeminocervical complex. Similarly, administration of the non-N-methyl-D-aspartate excitatory amino acid receptor blocker, GYKI 52466, lead to a dose-dependent inhibition of trigeminovascular-evoked responses in the trigeminocervical complex. These data demonstrate the participation of both N-methyl-D-aspartate- and non-N-methyl-D-aspartate-mediated mechanisms in transmission within the trigeminocervical complex, and suggest a clear preclinical role of glutamatergic mechanisms in primary headache syndromes, such as migraine and cluster headache.

I retract the 'relatively cheap' description of carnitine - was in a store yesterday that generally has good prices, and they had one bottle of carnosine for around $35 ... B-vitamins and choline seem more reasonable.

Monty...I buy all my stuff thru Puritans Pride online and they have 250 mg size buy 2 get 3 free at $39.98 (120 capsules) or 1000 mg buy 2 get 3 free for $71.98 (60 capsules)...so in essence you're getting 5 bottles (600 caps) for $39.98 of the 250 mg, etc. etc.  It's listed as Acetyl L-Carnitine (supporting memory and brain function). 
Just in case  you're interested:)

Monty, I forgot to ask...where are you in Florida?  I'm in the swamp as well.

grace wrote on Oct 23^rd, 2009 at 5:48am:

It's listed as Acetyl L-Carnitine (supporting memory and brain function).  Just in case  you're interested:)

Thanks - carnosine sounds like carnitine, but they are very different.  The acetyl-carnitine form is supposedly more absorbable than plain L-carnitine, but neither is carnosine.  I will check and see if carnitine has a similar effect.

Here's a study on homocysteine and migraine. Migraneurs have higher homocysteine levels than the general population. A 20% increase in homocysteine compared to average is associated with a 50% increase in the risk of migraines with aura, and a 50% increase in homocysteine is associated with a 600% increase in the risk for migraine with aura.  While it could be a correlation that is not related to the cause, we know that homocysteine is neurotoxic.

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I dunno, but I think it is all connected. These days I mainly wish I had applied myself and ventured into medics and microbiology. It annoys me alot to know there is a core in this and not being able to touch it because I do not have the qualifications. I acutally suggested to my wife yesterday that I want to restart and start medical school.

The only trouble is economy and my failing memory.
I haven´t totally put it out of my mind, but I realise it is a longshot.

Anyhows, what I wanted to say is that I have some sort of diffuse heartissues. I have a very long remission cycle (3-3.5 years) between my attacks.

Still, I have had these diffues heartproblems - diagnosis is that heart is fine - I know it isnt. It is laboured for some reason. I have had bronchitis - they say it is common in my age. I say it is a symptom. I say both of these are symptoms. I recently got myself tested.

Sure enough I had low testo levels, I had low GH levels. Both are in someway regulated by the hypthalamus. Low amounts could cause heart problems and inflammation diseases.

I am pissed. I really feel this whole can of shit is one an the same. My hypthalamus is not working as it should and it regulated all sort of stuff.
I am waiting for the first study that will say that CH sufferes live 10-30 years shorter than the average citizen.

Of course that could be a bliss... consifering. But I have children to take care of. I will do this headache for my entire life as long is does not stop me from supporting my children as I want to.