The 5-HT receptors are highly heterogeneous, broadly distributed, and classified into 7 different families on the basis of their amino acid sequences and other properties. The 5-HT 1 receptors are further subdivided according to their physiologic functions, binding affinity, and other features. The cloning of 5-HT 1 receptors and the development of 5-HT receptor agonists with specific affinity for 5-HT 1 receptor subtypes provided evidence for substantial populations of 5-HT 1B receptors on vascular endothelium and human meningeal blood vessels.
The triptans have at least 3 distinct modes of action, all of which may be additive in their antimigraine effects Table 1. Sumatriptan and rizatriptan have been shown to act selectively to cause vasoconstriction in isolated human middle meningeal arteries and are 10 times more potent in these arteries than in human coronary arteries.
However, given that there are some 5-HT 1B receptors in coronary arteries, triptans are contraindicated in patients with cerebrovascular or cardiovascular disease. The normalization of vessel diameter in cerebral arteries in migraineurs can be achieved without frank vasoconstriction through inhibition of CGRP release, and this mechanism may contribute to the relief of headache in patients treated with triptans. Studies in anesthetized rats demonstrate that rizatriptan has no direct vasoconstrictor effects, and blocks electrically stimulated dural vasodilation and plasma protein extravasation by inhibiting the release of CGRP via activation of prejunctional receptors located on trigeminal sensory nerve terminals.
The dilation of meningeal blood vessels may evoke a sensitization of central trigeminal neurons that may underlie the symptoms of headache and allodynia in migraineurs.
The triptans are also effective for migraine-associated symptoms, such as nausea, vomiting, photophobia, andphonophobia. A primary shortcoming of most triptans is headache recurrence. Significant differences in safety among the triptans have not been demonstrated, although the clinically used doses of naratriptan and almotriptan yield few adverse effects, producing a tolerability similar to that seen with placebo.
Typical adverse effects of the triptans are fatigue, dizziness, paresthesias, warm sensations, and neck, chest, and throat tightness. The tolerability of individual triptans is relative and cannot be predicted on the basis of lipophilicity, bioavailability, absolute dose size, or any combination of these variables.
The first triptan to be developed and approved for clinical use in patients with migraine was sumatriptan, which is available in injectable, intranasal, and oral formulations. The limitations of sumatriptan include low bioavailability, short plasma half-life, and low liposolubility.
These and other drawbacks prompted the development of triptans with improved pharmacokinetic properties. Rizatriptan has a rapid onset of action, high bioavailability, and a favorable adverse effects profile.
In direct comparisons of oral sumatriptan and rizatriptan in patients with migraine, 10 mg of rizatriptan had a slightly quicker time to headache relief in hazards ratio analysis against both the mg and mg doses of sumatriptan and better effects on several other secondary measures of efficacy, including reduction of functional disability and the proportion of patients who were pain free at 2 hours. Almotriptan is structurally related to sumatriptan, but its potency at the 5-HT 1D receptor is lower than that of sumatriptan, though its potency at the 5-HT 1B receptor is similar to that of sumatriptan and rizatriptan.
Frovatriptan has one of the highest affinities for the 5-HT 1B receptor and a long elimination half-life as long as 25 hours. This finding suggests that eletriptan has the potential for increased central nervous system concentrations and drug-drug interactions when coadministered with medications that are substrates or inhibitors of P-glycoprotein.
In addition, eletriptan is metabolized by the cytochrome P 3A4 system, and dose reduction may be mandated in the prescribing information when eletriptan is administered with medications that also are degraded by cytochrome P 3A4, such as macrolide antibiotics and antifungal medications.
Triptans are a major clinical advance in the treatment of migraine. The clinical efficacy of these drugs in migraine is related in part to their multiple mechanisms of action at vascular, neural, and central physiologic sites implicated in the pathophysiology of migraine.
These features underlie the beneficial effects of the triptans in patients with migraine, including rapid relief of headache and associated symptoms and improvements in productivity and health-related quality of life. Future studies may identify additional mechanisms of action of the triptans and the optimal role of these agents in the management of patients with migraine. Author contributions: Study concept and design Drs Tepper, Rapoport, and Sheftell ; acquisition of data Drs Tepper, Rapoport, and Sheftell ; analysis and interpretation of data Drs Tepper, Rapoport, and Sheftell ; drafting of the manuscript Drs Tepper, Rapoport, and Sheftell ; critical revision of the manuscript for important intellectual content Drs Tepper, Rapoport, and Sheftell ; statistical expertise Drs Tepper, Rapoport, and Sheftell.
Corresponding author and reprints: Stewart J. Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Table 1. View Large Download. Table 2. Hamel E Current concepts of migraine pathophysiology. Can J Clin Pharmacol. Google Scholar. Moskowitz MA Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci. Goadsby PJ Mechanisms and management of headache.
J R Coll Physicians Lond. Neurosci Lett. Fed Proc. Can J Neurol Sci. May AShepheard SLKnorr M et al Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine. Clin Auton Res. Prog Drug Res. Ann N Y Acad Sci. Hamel E The biology of serotonin receptors: focus on migraine pathophysiology and treatment.
Eur J Pharmacol. Goadsby PJ Serotonin receptors and the acute attack of migraine. Clin Neurosci. Receptors Channels. Brain Res. Longmore JRazzaque ZShaw D et al Comparison of the vasoconstrictor effects of rizatriptan and sumatriptan in human isolated cranial arteries: immunohistological demonstration of the involvement of 5-HT 1B -receptors.
Br J Clin Pharmacol. Longmore JHargreaves RJBoulanger CM et al Comparison of the vasoconstrictor properties of the 5-HT 1D -receptor agonists rizatriptan MK and sumatriptan in human isolated coronary artery: outcome of two independent studies using different experimental protocols.
Funct Neurol. J Neurosci. Br J Pharmacol. Ann Neurol. Not Available Axert tablets. In: Medical Economics Inc, eds. Physicians' Desk Reference. However, if your symptoms do not improve after you take sumitriptan, do not take a second tablet without calling your doctor. Your doctor will tell you the maximum number of tablets you may take in a hour period.
Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take sumatriptan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. You may take your first dose of sumatriptan in a doctor's office or other medical facility where you can be monitored for serious reactions.
Call your doctor if your headaches do not get better or occur more frequently after taking sumatriptan. If you take sumatriptan more often or for longer than the recommended period of time, your headaches may get worse or may occur more frequently. You should not take sumatriptan or any other headache medication for more than 10 days per month. Call your doctor if you need to take sumatriptan to treat more than four headaches in a 1-month period.
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information. Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature, away from excess heat and moisture not in the bathroom. Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them.
However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program.
It is important to keep all medication out of sight and reach of children as many containers such as weekly pill minders and those for eye drops, creams, patches, and inhalers are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location — one that is up and away and out of their sight and reach. In case of overdose, call the poison control helpline at If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at You should keep a headache diary by writing down when you have headaches and when you take sumatriptan.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription. It is important for you to keep a written list of all of the prescription and nonprescription over-the-counter medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Sumatriptan pronounced as soo ma trip' tan. Why is this medication prescribed? How should this medicine be used? Other uses for this medicine What special precautions should I follow?
0コメント