Serotonin reuptake inhibitor
Question:
Is lack of serotonin in the brain implicated in migraine headaches and is this related to the hole in the heart situation? My understanding is that virtually any anti-depressant raises the pain threshold, thus having the potential to relieve migraine. Elavil (amitriptyline) is one of the most often prescribed. I don’t know if serotonin and SSRIs are specific factors.
According to current migraine theory, it’s not the serotonin per se, that is the key, but the receptor subtype where the serotonin is present. The "triptans", as an example, are all serotonin agonists, but are targeted at the serotonin receptor subtype: 5HT-1d(alpha), which is concentrated in a specific location (the trigeminalvascular junction). This fits in nicely with the trigeminalvascular theory of migraine. Blood levels of serotonin say NOTHING about its "distribution" in the body and brain, which is what is deemed medically relevant to migraine. SSRIs also increase serotonin in the synapse, but I do not remember their target receptor, and cannot imagine it being the same as a triptan. Finally, triptans are not COMPLETELY without affect at other serotonin receptor subtypes. Drugs are said to have an "affinity" for different receptor subtypes, and this can be quantified in animals. With migraine drugs, one challenge was to increase the affinity of a drug toward the target, WITHOUT mimicking serotonin at other serotonin receptors, particularly in the heart—where vasoconstriction is NOT desirable. Vasoconstriction is an affect of serotonin on blood vessels, but it is still an open question as to whether or not it is the affect responsible for efficacy in aborting a migraine. The triptans have an affinity for their target that is vastly greater than in the heart’s coronary arteries, but I’m sure that many of you remember questioning chest discomforts when taken triptans. I know of no evidence that these are coronary events, and it’s been intensively studied, but the warnings against heart patients using them persists, probably for good reason, as receptor distribution is largely genetic, and there are some rare phenotypes in the general population. Given that these meds. are not "absolutely" specific to their target, anything can happen, but rarely does. I’m not familiar with the "hole in the heart" that you refer to in your post. Jack
Response:
Is lack of serotonin in the brain implicated in migraine headaches and is this related to the hole in the heart situation?
My understanding is that virtually any anti-depressant raises the pain threshold, thus having the potential to relieve migraine. Elavil (amitriptyline) is one of the most often prescribed. I don’t know if serotonin and SSRIs are specific factors.
Response:
I used to have frequent migraines but since I started taking serotonin reuptake inhibitors like Prozac (for obsessive compulsive disorder) I hardly ever get a migraine. When I do get an occasional migraine I just take Excedrine Migraine.Is lack of serotonin in the brain implicated in migraine headaches and is this related to the hole in the heart situation?
Response:
This is new to me and very interesting. I’ll try to find some time soon to research it. Thanks for the post. Jack – Hide quoted text — Show quoted text – The "hole in the heart" deals with some research which has been printed recently. It deals with PFO (patent foramen ovale) or a hole in the heart. See http://www.sciencenews.org/articles/20050219/bob8.asp This is the part that mentioned serotonin "Nevertheless, researchers are excited by the possibility that PFOs cause some migraines. Wilmshurst speculates, "We think the PFO permits a substance that would be filtered in the lungs to get to the brain." He and some other researchers suspect the peptide serotonin, which is neurologically active and doesn’t usually circulate in blood heading from the heart to the brain." http://www.usnews.com/usnews/health/articles/050411/11migraine.htm http://www.newscientist.com/article.ns?id=dn4113 (Sept. 2003) http://www.thepittsburghchannel.com/healthcast/4537586/detail.html http://wcco.com/topstories/local_story_155211030.html http://www.thepittsburghchannel.com/health/4537586/detail.html http://www.sc.mahidol.ac.th/sclg/supports/ors147/md/p32.htm http://www.owendot.com/cgi-bin/avpub/config.pl/frames=n/read/7731 ‘did
Response:
Jack, thanks for that very thorough and helpful response. I don’t think I ever quite understood the whole thing. This gave me a whole lot more understanding about how the serotonin and the triptans work. Michelle
– Hide quoted text — Show quoted text – Is lack of serotonin in the brain implicated in migraine headaches and is this related to the hole in the heart situation? My understanding is that virtually any anti-depressant raises the pain threshold, thus having the potential to relieve migraine. Elavil (amitriptyline) is one of the most often prescribed. I don’t know if serotonin and SSRIs are specific factors. According to current migraine theory, it’s not the serotonin per se, that is the key, but the receptor subtype where the serotonin is present. The "triptans", as an example, are all serotonin agonists, but are targeted at the serotonin receptor subtype: 5HT-1d(alpha), which is concentrated in a specific location (the trigeminalvascular junction). This fits in nicely with the trigeminalvascular theory of migraine. Blood levels of serotonin say NOTHING about its "distribution" in the body and brain, which is what is deemed medically relevant to migraine. SSRIs also increase serotonin in the synapse, but I do not remember their target receptor, and cannot imagine it being the same as a triptan. Finally, triptans are not COMPLETELY without affect at other serotonin receptor subtypes. Drugs are said to have an "affinity" for different receptor subtypes, and this can be quantified in animals. With migraine drugs, one challenge was to increase the affinity of a drug toward the target, WITHOUT mimicking serotonin at other serotonin receptors, particularly in the heart—where vasoconstriction is NOT desirable. Vasoconstriction is an affect of serotonin on blood vessels, but it is still an open question as to whether or not it is the affect responsible for efficacy in aborting a migraine. The triptans have an affinity for their target that is vastly greater than in the heart’s coronary arteries, but I’m sure that many of you remember questioning chest discomforts when taken triptans. I know of no evidence that these are coronary events, and it’s been intensively studied, but the warnings against heart patients using them persists, probably for good reason, as receptor distribution is largely genetic, and there are some rare phenotypes in the general population. Given that these meds. are not "absolutely" specific to their target, anything can happen, but rarely does. I’m not familiar with the "hole in the heart" that you refer to in your post. Jack
Response:
You’re welcome. But, remember, this is only one theory and there are others. In a decade or so, this may all need revision as that has been the usual case with migraine. It’s been very difficult to get a handle on the underlying mechanism(s) behind an extremely profound and complex problem. Why, for instance, does sumatriptan work at all, as it doesn’t cross the blood/brain barrier? The pro-Imitrex group has stretched long and hard to come up with a barely plausible (IMHO) and theoretical migraine is fully developed before taking Imitrex" to "take Imitrex at the first sign of a migraine". OTOH, Zomig does cross the barrier, and the pro-Zomig interests have tried to heavily exploit this fact. But, explanations of its efficacy also have problems. That’s for another day. Jack – Hide quoted text — Show quoted text – Jack, thanks for that very thorough and helpful response. I don’t think I ever quite understood the whole thing. This gave me a whole lot more understanding about how the serotonin and the triptans work. Michelle Is lack of serotonin in the brain implicated in migraine headaches and is this related to the hole in the heart situation? My understanding is that virtually any anti-depressant raises the pain threshold, thus having the potential to relieve migraine. Elavil (amitriptyline) is one of the most often prescribed. I don’t know if serotonin and SSRIs are specific factors. According to current migraine theory, it’s not the serotonin per se, that is the key, but the receptor subtype where the serotonin is present. The "triptans", as an example, are all serotonin agonists, but are targeted at the serotonin receptor subtype: 5HT-1d(alpha), which is concentrated in a specific location (the trigeminalvascular junction). This fits in nicely with the trigeminalvascular theory of migraine. Blood levels of serotonin say NOTHING about its "distribution" in the body and brain, which is what is deemed medically relevant to migraine. SSRIs also increase serotonin in the synapse, but I do not remember their target receptor, and cannot imagine it being the same as a triptan. Finally, triptans are not COMPLETELY without affect at other serotonin receptor subtypes. Drugs are said to have an "affinity" for different receptor subtypes, and this can be quantified in animals. With migraine drugs, one challenge was to increase the affinity of a drug toward the target, WITHOUT mimicking serotonin at other serotonin receptors, particularly in the heart—where vasoconstriction is NOT desirable. Vasoconstriction is an affect of serotonin on blood vessels, but it is still an open question as to whether or not it is the affect responsible for efficacy in aborting a migraine. The triptans have an affinity for their target that is vastly greater than in the heart’s coronary arteries, but I’m sure that many of you remember questioning chest discomforts when taken triptans. I know of no evidence that these are coronary events, and it’s been intensively studied, but the warnings against heart patients using them persists, probably for good reason, as receptor distribution is largely genetic, and there are some rare phenotypes in the general population. Given that these meds. are not "absolutely" specific to their target, anything can happen, but rarely does. I’m not familiar with the "hole in the heart" that you refer to in your post. Jack
Response:
Yes, interesting. Zomig is my drug of choice and seems to be the best of all I have. Relpax is my close second…at least of the triptans. Michelle
– Hide quoted text — Show quoted text – You’re welcome. But, remember, this is only one theory and there are others. In a decade or so, this may all need revision as that has been the usual case with migraine. It’s been very difficult to get a handle on the underlying mechanism(s) behind an extremely profound and complex problem. Why, for instance, does sumatriptan work at all, as it doesn’t cross the blood/brain barrier? The pro-Imitrex group has stretched long and hard to come up with a barely plausible (IMHO) and theoretical explanation. This developed before taking Imitrex" to "take Imitrex at the first sign of a migraine". OTOH, Zomig does cross the barrier, and the pro-Zomig interests have tried to heavily exploit this fact. But, explanations of its efficacy also have problems. That’s for another day. Jack Jack, thanks for that very thorough and helpful response. I don’t think I ever quite understood the whole thing. This gave me a whole lot more understanding about how the serotonin and the triptans work. Michelle Is lack of serotonin in the brain implicated in migraine headaches and is this related to the hole in the heart situation? My understanding is that virtually any anti-depressant raises the pain threshold, thus having the potential to relieve migraine. Elavil (amitriptyline) is one of the most often prescribed. I don’t know if serotonin and SSRIs are specific factors. According to current migraine theory, it’s not the serotonin per se, that is the key, but the receptor subtype where the serotonin is present. The "triptans", as an example, are all serotonin agonists, but are targeted at the serotonin receptor subtype: 5HT-1d(alpha), which is concentrated in a specific location (the trigeminalvascular junction). This fits in nicely with the trigeminalvascular theory of migraine. Blood levels of serotonin say NOTHING about its "distribution" in the body and brain, which is what is deemed medically relevant to migraine. SSRIs also increase serotonin in the synapse, but I do not remember their target receptor, and cannot imagine it being the same as a triptan. Finally, triptans are not COMPLETELY without affect at other serotonin receptor subtypes. Drugs are said to have an "affinity" for different receptor subtypes, and this can be quantified in animals. With migraine drugs, one challenge was to increase the affinity of a drug toward the target, WITHOUT mimicking serotonin at other serotonin receptors, particularly in the heart—where vasoconstriction is NOT desirable. Vasoconstriction is an affect of serotonin on blood vessels, but it is still an open question as to whether or not it is the affect responsible for efficacy in aborting a migraine. The triptans have an affinity for their target that is vastly greater than in the heart’s coronary arteries, but I’m sure that many of you remember questioning chest discomforts when taken triptans. I know of no evidence that these are coronary events, and it’s been intensively studied, but the warnings against heart patients using them persists, probably for good reason, as receptor distribution is largely genetic, and there are some rare phenotypes in the general population. Given that these meds. are not "absolutely" specific to their target, anything can happen, but rarely does. I’m not familiar with the "hole in the heart" that you refer to in your post. Jack
Response:
I used to have frequent migraines but since I started taking serotonin reuptake inhibitors like Prozac (for obsessive compulsive disorder) I hardly ever get a migraine. When I do get an occasional migraine I just take Excedrine Migraine.Is lack of serotonin in the brain implicated in migraine headaches and is this related to the hole in the heart situation?
I also have OCD. OCD raises the stress levels dramatically and stress can be a major contributor to migraines. I had chronic migraines for over two months before I was able to get my OCD under control with Seroquel. It was almost a night and day difference and my migraines went from Chronic to almost nothing in about 48 hrs. Erik
