how do serotonin-agonists work in the treatment of migraine headaches?

Serotonin receptors have been found on the trigeminal nerve and cranial vessels and their agonists especially triptans prove effective in migraine treatment. It has been found that triptans act on trigeminovascular system and bring the elevated serum levels of key molecules like calcitonin gene related peptide (CGRP

) to normal.

Full Answer

What is the role of serotonin in migraine headaches?

Changes in serotonin may precede the vascular and muscular changes of migraine and tension-type headaches. The influence of serotonin on headaches explains a number of clinical situations that affect headache activity and the variety of classes of effective headache medications.

Do drugs for migraine interact with serotonin receptors?

Adding to the enigma it is apparent that many of the presently available drugs for the treatment of migraine interact in one way or another with serotonin receptors. However, they tend to have a number of other unrelated actions and they are only of limited clinical value.

How do medications treat migraines?

But if they don't, your doctor may suggest you try a triptan drug. This kind of medicine can't keep migraine headaches from happening. But it can treat your headache once it starts. Your doctor may give you triptan tablets you'll take by mouth. You also could get it as a nasal spray or shot. Most people feel better within 2 hours of taking it.

What is the future of serotonergic migraine drugs?

Outside of new formulations of drugs classically used for migraine, such as inhaled dihydroergotamine or triptans [67, 68], the future of serotonergic migraine drugs lies most clearly with selective 5HT1fagonists (e.g. lasmitidan [69]).

How do serotonin receptor agonists work in the treatment of migraine headaches?

How Do They Work? Triptan drugs work like a brain chemical called serotonin. This helps quiet down overactive pain nerves. In other words, triptans reverse the changes in your brain that caused your migraine.

How is serotonin involved in migraine?

Various studies have implicated serotonin in the pathogenesis of migraine. Serotonin vasoconstricts the nerve endings and blood vessels and in this way affects nociceptive pain. Comings43 postulated that low serotonin levels dilate blood vessels and initiate migraine.

Does serotonin treat migraines?

An injection of serotonin during an attack decreases migraine symptoms but is associated with many unpleasant adverse effects.

What is the mechanism of action of serotonin receptor agonist?

Mechanism of Action: A serotonin receptor agonist that binds selectively to vascular receptors, producing a vasoconstrictive effect on cranial blood vessels. Therapeutic Effect: Produces relief of migraine headache.

What do serotonin antagonists do?

Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine.

Are triptans serotonin agonists?

The triptans are serotonin agonists with high affinity for the 5-HT1B and 5-HT1D receptors which are found on smooth-muscle cells of blood vessels. Simulation of the 5-HT1D receptor results in constriction of intracranial blood vessels.

How do antidepressants work for migraines?

How do tricyclic antidepressants help prevent migraine? During a migraine attack, doctors believe that your serotonin levels plummet. Tricyclic antidepressants help prevent attacks from happening as frequently by maintaining a healthy serotonin level.

Which serotonin receptor antagonist is used in migraine?

Zolmitriptan (Zomig, Zomig-ZMT) A selective agonist for serotonin 5-HT1B/1D receptors in cranial arteries, zolmitriptan suppresses the inflammation associated with migraine headaches.

Does lack of serotonin cause migraines?

What causes migraine? The exact cause of migraine is unknown, but may be related to low brain levels of an important chemical called serotonin. During an attack, changes in brain activity may cause blood vessels and nerves around the brain to become inflamed. Many women have attacks linked to their menstrual cycles.

What happens when serotonin receptors are activated?

Serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation.

Do serotonin agonists increase serotonin?

5-HT2B receptor agonists MDMA has been reported to be both a potent direct agonist and have an indirect effect by increasing plasma serotonin levels.

What happens when serotonin binds to its receptor?

Serotonin binds to the portion of the receptor on the outside of the cell (shown here at the top of the picture). This induces subtle changes in the shape of the protein and sends a signal to G proteins inside the cell.

How do triptans work?

It is clear that triptans act at the cellular level by activating 5HT1b/1dand in some cases 5HT1freceptors, but many questions remain about their mechanism of action. One major unresolved question in the field, despite over 20 years of use, is where and how they act [27]. The best recognized mechanism of action of triptans is vasoconstriction [28], a mechanism targeted since vasodilation has long been thought to contribute to migraine. Using magnetic-resonance angiography of intra-and extra-cranial vessels in migraine patients, studies have both shown [29] and not shown vasodilation during migraine [30]. However, both of these studies used provocative vasodilatory agents to elicit migraines. A more recent study with patients experiencing spontaneous attacks found no extracranial vasodilation and only a small degree of intracranial vasodilation [31**], leading the authors to conclude that vasodilation is not the cause of migraine. If there is no vasodilation during natural migraines, the efficacy of triptans is likely due to action on neurons.

What is migraine headache?

Migraine is a complex neurological disorder most notably characterized by intense unilateral throbbing headache but also consists of associated symptoms such as nausea, vomiting, photo- and phonoallodynia (pain caused by light/sound), cutaneous hypersensitivity, aura, and changes in mood or energy levels. The 2012 Global Burden of Disease study by the The Lancet placed migraine as the 8thmost burdensome disease on the planet and the 4thmost in women [1], as migraine is approximately 3 times more prevalent in females. Studies on the pathophysiology of migraine have examined potential mechanisms in the trigeminovascular system as well as a variety of brain and brainstem regions [2–5] but the pathophysiology remains poorly understood.

Do triptans affect the brain?

Whether triptans require access to sites in the brain to produce their actions is not clear [38]. Asghar and colleagues found no change in blood-oxygen-level-dependent (BOLD) signal (an imaging technique that measures blood flow and oxygenated hemoglobin movement as a surrogate for neuronal activity) in the visual cortex of humans after sumatriptan dosing in healthy volunteers [39]. In contrast, a pharmaco-fMRI study showed activation of several pain-related brain regions after dosing sumatriptan in healthy volunteers [40] and thus triptan activity in the brain may be region specific. However, the critical site of action of triptans in the brain is still not known. Prior reports of possible CNS triptan action in the periaqueductal grey (PAG; [41]) have been extended with a recent finding showing that endocannabinoids in the PAG modulate meningeal afferent traffic in the brainstem and these actions are mediated by PAG 5HT1b/1dreceptors [42*]. Triptans have also been proposed to work in other brain regions [43–45], but recent studies have further implicated serotonergic activity in the hypothalamus as capable of modulating nociceptive input in the trigeminal nucleus caudalis. After lesioning the A11 nucleus of the hypothalamus, Charbit and colleagues found increased activity in nucleus caudalis neurons receiving meningeal input and this increase was attenuated by intravenous naratriptan [46]. A subsequent study found that microinjection of naratriptan directly into the paraventricular nucleus of the hypothalamus decreased the activity of caudalis neurons both basally and in response to meningeal stimulation [47**]. These studies implicate a serotonergic descending component from the hypothalamus to the brainstem that may modulate noxious input and may also contribute to the efficacy of triptans. Given the suggested role of the hypothalamus in migraine pathophysiology [48–50], potential triptan actions in this brain region add to the possible mechanisms of action of these drugs. Better understanding of which brain regions are necessary for triptan efficacy, or even whether CNS activity is required, will greatly aid in the development of new migraine therapeutics.

Does 5HT work for migraines?

Given the clear efficacy of serotonergic drugs for migraine, continued study on the role of the endogenous 5HT system may lead to more novel therapies. And with the list of studies demonstrating efficacy triptans in models of non-headache, clinical studies should address whether these drugs work for other types of pain.

Do migraines have 5HT?

Markers of 5HT levels in the brains of migraine patients show no changes between attacks. Several recent meta-analyses show the most convincing data on genetic differences in the serotonergic system for 5HT transporters. Findings of additional triptan actions on peripheral trigeminovascular neurons and in the hypothalamus add more fuel to the debate on where these drugs act. A growing list of studies show efficacy of multiple triptans and other 5HT1b/1dagonists in pre-clinical models of non-headache pain arguing for reevaluation of whether these drugs have efficacy in other pain states. Despite these issues, serotonergic drugs continue to be the gold standard for abortive agents with new members on the horizon (5HT1fagonists).

Can triptans be used for migraine?

The efficacy of triptans for migraine indicates a role for the serotonergic system in the treatment of this disorder. Outside of new formulations of drugs classically used for migraine , such as inhaled dihydroergotamine or triptans [67, 68], the future of serotonergic migraine drugs lies most clearly with selective 5HT1fagonists (e.g. lasmitidan [69]). Some triptans have efficacy at this receptor but several studies have shown that selective agonists of 5HT1fhave efficacy in preclinical migraine models and more importantly, several clinical trials have demonstrated efficacy of these drugs as abortive agents for migraine (reviewed recently by [70–72]). And although these drugs have been proposed to act centrally, the selective 5HT1fagonist LY-344864 inhibited evoked CGRP release from isolated dural tissue with efficacy similar to sumatriptan [73] so a peripheral mechanism cannot be ruled out. Future studies will determine whether these agents have efficacy and tolerability equal to or greater than triptans but they may ultimately find a place in the treatment toolbox due to their lack of vascular issues and cardiovascular risk.

Does triptan affect trigeminal neurons?

Recent studies have further documented the actions of triptans on primary afferent trigeminal neurons. Sumatriptan was found to modulate ionic currents in dural-projecting trigeminal neurons in vitroincluding voltage-gated calcium currents (confirming an earlier report [32]) and now demonstrating modulation of potassium currents [33*]. This drug also inhibited calcium influx in individual neuronal fibers in the dura via calcium channel modulation [34]. Sumatriptan was found to inhibit the capsaicin/noxious heat/proton-sensitive transient receptor potential channel vanilloid 1 (TRPV1) in trigeminal neurons [35*], consistent with other reports where sumatriptan inhibited both cytokine production in response to capsaicin [36] and capsaicin-induced CGRP release from trigeminal neurons [37]. Thus, one potential non-vascular mechanism of action is via triptan modulation of various ionic currents on trigeminal afferents that carry pain information from the meninges.

Why did Sacks lose his ability to hear music?

Sacks was able to understand speech and to interpret other sounds, but just before his headache started, he suddenly (and temporarily) lost his ability to hear music as music. The neurotransmitter serotonin plays a key role in migraine. The usual sequence of events that lead to a migraine headache run something like this:

What is migraine headache?

Migraine headaches are among the most mysterious of all neurological events. They may cause days of excruciating pain, minutes of minor pain, or no pain at all. They may strike some people at the happiest moments of their lives, and other people at the most depressed moments of their lives.

What are the triggers of migraines?

There are probably as many different triggers for migraine headaches as there are people who have migraine headaches, but common triggers include changes in work schedule, loss of sleep, exercise, sexual intercourse, noxious fumes, cigarette smoke, changes in weather, and changes in hormone levels. The brain responds by using large amounts ...

What causes blood vessels to dilate?

Serotonin causes blood vessels to constrict, but a shortage of serotonin causes blood vessels to dilate. The massive depletion of serotonin causes blood vessels leading to the brain to dilate, expanding, loosening, and leaking plasma into surrounding tissues.

What foods should I avoid with tyramine?

Avoid foods that contain large amounts of the amino acid tyramine, such as hard cheeses, smoked fish, chocolate, salami and other fermented meats, anchovies, Worcestershire sauce (which is made with anchovies), fava beans, pickled herring, and red wine. The tyramine in these foods blocks the transport of tryptophan into the brain, which the brain uses to make serotonin.

Does aspirin help with migraines?

Consider taking aspirin. It's probably true that most of the time "An aspirin a day keeps the migraines away," but when you stop taking aspirin, you may get an exceptionally severe migraine.

Can serotonin help with migraines?

Serotonin and migraine treatment. Your doctor probably can give you a medication that is at least partially successful at helping the neurons of your brain conserve serotonin so that migraine headaches are less likely. Many of the treatments for migraine are also treatments for depression. ( You might also be interested in herbal cure ...

What is the role of triptans in the trigeminovascular system?

It has been found that triptans act on trigeminovascular system and bring the elevated serum levels of key molecules like calcitonin gene related peptide (CGRP) to normal. Currently CGRP receptor antagonists, olcegepant and telcagepant are under consideration for antimigraine therapeutics.

What is migraine headache?

Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular disorder involving local vasodilation of intracranial, extracerebral blood vessels ...

Does serotonin affect migraines?

At the same time, decreased levels of neurotransmitter, serotonin have been observed in migraineurs. Serotonin receptors have been found on the trigeminal nerve and cranial vessels and their agonists especially triptans prove effective in migraine treatment.

Is migraine a CGRP?

Serotonin and CGRP in migraine. Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular disorder involving local vasodilation of intracrani ….

Is migraine a neurovascular disorder?

It is primarily a complex neurovascular disorder involving local vasodilation of intracrani …. Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular ...

Is migraine a neurologic disorder?

Migraine has long been considered as a "vascular headache" but clearly neurological mechanisms are involved. The pathophysiology appears to somehow involve serotonin, both peripherally and centrally, but its involvement may be just epiphenomenal. Adding to the enigma it is apparent that many of the presently available drugs for the treatment of migraine interact in one way or another with serotonin receptors. However, they tend to have a number of other unrelated actions and they are only of limited clinical value. Interestingly a promising new drug for the treatment of the acute attack, sumatriptan, has a very selective action as an agonist at a specific 5-HT1-like receptor sub-type, mediating vasoconstriction, which is localized on cranial blood vessels. Its action may, or may not, be independent of any involvement of serotonin in the genesis of migraine. Hopefully though, current attempts to determine sumatriptan's mechanism of action will shed further light on the pathology of migraine itself and the putative involvement of serotonin.

Is sumatriptan a selective agonist?

Interestingly a promising new drug for the treatment of the acute attack, sumatriptan, has a very selective action as an agonist at a specific 5-HT1-like receptor sub-type, mediating vasoconstriction, which is localized on cranial blood vessels.

How many journal articles describe the relationship between serotonin and headache?

Data sources: Fifty-four journal articles that described a relationship between serotonin and headache in animal and human models were identified through Medline search and bibliography and reviewed. Alterations in serotonin, headache, and clinical situations influencing headache activity were examined.

Does headache cause muscle contraction?

Data synthesis: Abnormalities in blood vessels have traditionally been implicated in the pathogenesis of migraine headaches, and excessive muscle contraction in tension-type headaches. Interestingly, both vascular and muscular changes occur in both migraine and tension-type headache. Recently, biochemical changes have been demonstrated in both types of headaches. These biochemical changes are postulated to precede and possibly cause the subsequent changes in blood vessels and muscle tone, known to occur in chronic headaches. Serotonin has been the most widely studied neurochemical in relation to headaches. Apparently contradictory results have been shown, such as increasing serotonin levels both increasing and decreasing headaches.