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Sleep, serotonin and indole-ring compounds (Read 2491 times)
Ungweliante
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Sleep, serotonin and indole-ring compounds
Nov 25th, 2008 at 10:32am
 
As some of you might know, I've been studying to get into the medical university for some time now. Today, when reading about sleep, I stumbled upon something I considered particularly interesting.

"The raphe-nuclei secrete serotonin and are most active when a person is awake. Their activity diminishes when a person is falling asleep and almost totally stops when a person is in REM-sleep."

Now, serotonin is a powerful vasoconstrictor, which means that it constricts blood-vessels. Thus going into REM-sleep basically means that the blood-vessels dilate, because there will be far less serotonin around.

Also serotonin has a chemical structure very similar to the various indole-ring compounds, e.g. those contained by RC-seeds and such.

A lot of you guys (but not all) get the worst attacks when asleep, and this is probably one mechanism which is responsible for that. To think of how a person might apply this knowledge to use, I would think that those people who get the worst attacks when they are asleep would be the ones who would probably benefit from RC-seeds or their "cousins".

- Best regards and PFDAN,
Rosa
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Bob Johnson
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Re: Sleep, serotonin and indole-ring compounds
Reply #1 - Nov 26th, 2008 at 8:07am
 
The implications of these comments are interesting to consider:

Interesting to note that he is saying that the primary mode of action is NOT as a vasoconstrictor but on its effect on the central nervous system. Doesn't change our appreciation of this class of meds but suggests we need to change how we think about the nature of CH.
==============================
Handb Exp Pharmacol. 2007;(177):129-43.   


Serotonin receptor ligands: treatments of acute migraine and cluster headache.

Goadsby PJ.

Institute of Neurology, Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk

Fuelled by the development of the serotonin 5-HT(1B/1D) receptor agonists, the triptans, the last 15 years has seen an explosion of interest in the treatment of acute migraine and cluster headache. Sumatriptan was the first of these agonists, and it launched a wave of therapeutic advances. These medicines are effective and safe. Triptans were developed as cranial vasoconstrictors to mimic the desirable effects of serotonin, while avoiding its side-effects. IT HAS SUBSEQUENTLY BEEN SHOWN THAT THE TRIPTANS' MAJOR ACTION IS NEURONAL, WITH BOTH PERIPHERAL AND CENTRAL TRIGEMINAL INHIBITORY EFFECTS, AS WELL AS ACTIONS IN THE THALAMUS AND AT CENTRAL MODULATORY SITES, SUCH AS THE PERIAQUEDUCTAL GREY MATTER. Further refinements may be possible as the 5-HT(1D) and 5-HT(1F) receptor agonists are explored. Serotonin receptor pharmacology has contributed much to the better management of patients with primary headache disorders.

PMID: 17087122 [PubMed]
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Re: Sleep, serotonin and indole-ring compounds
Reply #2 - Nov 26th, 2008 at 8:35am
 
I have also read, that right before a clusterheadache or migraine attack, there is a serotonin storm in the brain. Large amounts of serotonin released into the bloodstream constricts the bloodvessels and then suddenly it's gone. What happens then? Major bloodvessel dilation seems to be the logical answer...
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MITYRARE
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Re: Sleep, serotonin and indole-ring compounds
Reply #3 - Nov 26th, 2008 at 9:14am
 
My neuro agrees that REM sleep is not where a CH sufferers should be and has for many years prescribed CH sufferers medications for sleep that quickly get you past REM into a deeper sleep pattern than REM which is not restful.  It is theorised that many CH begin during REM sleep....now maybe your expanation explains why.
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coach_bill
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Re: Sleep, serotonin and indole-ring compounds
Reply #4 - Nov 26th, 2008 at 2:19pm
 
Thanks for all this info.. But can someone explain this like i was still in 5th grade. I understand the rem sleep part. But the vasconstricter part im lost Huh so the blood vessels shrink, and the serention stops?? Ht5 vs h1?? then we get the CH ?? So then seeds are like serentioin so we dont get the CH ?? sorry. Undecided Coach Bill
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boy i cant wait till it's my turn to give him a headache. paybacks a bitch
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Garys_Girl
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Re: Sleep, serotonin and indole-ring compounds
Reply #5 - Nov 29th, 2008 at 8:27pm
 
Coach Bill:

Before answering your question, I think it is REALLY important to note that

1) the mechanism of action in cluster headaches is not known
2) All primary headaches had been thought to be caused by chemical factors alone ("The dogma is that primary headache, like cluster headaches and migraine, are due to abnormal brain function with completely normal brain structure," Dr. Goadsby), BUT
3) using a new scanning technique (in 1999) Dr. Goadsby has shown that cluster headaches are likely to be caused by excessive growth of grey cells in one part of the brain (the hypothalamus),
4) "Professor Goadsby said, 'We also found that the area of the brain where these structural abnormalities were seen, the hypothalamus, is the same area of the brain where the functional studies show that activity is abnormal during the headache state.  This complete correlation of functional and structural abnormality is striking.' "  Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

When it comes to the functional abnormalities, most of the cluster headache treatments are actually treatments developed for Migraines: most of those act on serotonin receptors.

"The precise cause of migraine headaches is still not fully understood [either], but it is generally believed that the key element in understanding them has to do with the blood flow changes in the brain," ...which Rosa was addressing.

Here's how that works:  Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

[Some trigger] "creates a spasm in the nerve-rich arteries at the base of the brain.  This spasm closes down or constricts several arteries supplying blood to the brain, thus reducing blood flow to the brain.  Simultaneously, platelets clump together and are believed to release a chemical called serotonin.  (The trigeminal [5th cranial] nerve has been implicated.)

The serotonin causes the blood vessels in the head to contract and lowers the pain threshold.  Before a migraine episode, serotonin levels have been detected to be unusually high in the brain, lending weight to the previous explanation.  During a migraine attack, serotonin levels become very low.  The low amounts cause the blood vessels to be unusually large...."

It is this basic vasodilation that is addressed by the triptans (which cause vasoconstriction), caffeine (which causes vasoconstriction), and oxygen (which causes vasoconstriction).  Obviously each has a different mechanism of action, which is why they work for some people and not for others.

It is because the indole-ring compounds (such as LSD, LSA, psilocybin, Kudzu, &etc) have very similar chemical structure to serotonin that those researching psychedelics in the treatment of cluster headaches decided to explore that avenue. 

Rosa is pointing out that there appears to be a relationship between sleep & serotonin levels (and thus the issues of vasodilation at night) that indicates that especially those with primarily night-time hits may respond better to treatment with indole-ring type compounds than other types of treatment.  (I think).

Laurie



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Re: Sleep, serotonin and indole-ring compounds
Reply #6 - Nov 29th, 2008 at 8:32pm
 
coach_bill wrote on Nov 26th, 2008 at 2:19pm:
Thanks for all this info.. But can someone explain this like i was still in 5th grade. I understand the rem sleep part. But the vasconstricter part im lost Huh so the blood vessels shrink, and the serention stops?? Ht5 vs h1?? then we get the CH ?? So then seeds are like serentioin so we dont get the CH ?? sorry. Undecided Coach Bill


Yes, LSA, LSD and psilocybin are like serotonin:  From the Cluster Buster's site:

"The Theory of Hallucinogens as a Treatment for Cluster Headaches

The hallucinogenic substances are close enough to serotonin in structure that they fool serotonin receptors into bonding with them...."

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Laurie
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coach_bill
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Re: Sleep, serotonin and indole-ring compounds
Reply #7 - Nov 29th, 2008 at 8:41pm
 
Laurie, Thank you for all that info and the links to the website. I do have a better understanding now of the workings of this. I get mine mostly at night untill its out of control by week 4. Once again thank you all for this info and thats for this website.. Coach Bill
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boy i cant wait till it's my turn to give him a headache. paybacks a bitch
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