Disease relevance of Triptan

• Triptan medications to treat acute migraine [1].
• Although patients overusing ergots and analgesics typically had a daily tension-type headache, patients with triptan-induced MOH were more likely to describe a (daily) migraine-like headache or an increase in migraine frequency [2].
• In a mouse model of pneumococcal meningitis, survival and clinical score at 24 hours were significantly improved by triptan treatment [3].
• In parallel with triptan administration, acting via 5-HT(1B/1D) receptors, head pain subside and neuropeptide release normalise [4].
• There was no increase in risk of myocardial infarction with current (adjusted RR 0.80, 95% CI 0.58-1.11) or recent (adjusted RR 1.15, 95% CI 0.71-1.87) triptan use [5].

Psychiatry related information on Triptan

• We describe a case of status migrainosus precipitated by electroconvulsive therapy (ECT) that was refractory to treatment with triptan medications but which resolved with dihydroergotamine (DHE) [6].

High impact information on Triptan

• Rather, triptan action appears to be exerted through presynaptic 5HT(1B/1D) receptors in the dorsal horn to block synaptic transmission between axon terminals of the peripheral trigeminovascular neurons and cell bodies of their central counterparts [7].
• The early treatment results suggest that triptan action provides a powerful means of preventing the initiation of central sensitization triggered by chemical stimulation of meningeal nociceptors [8].
• Zolmitriptan was the only triptan that decreased temporal artery diameter significantly (by 12% +/- 3%, P < .001) [9].
• Eletriptan (Relpax) is an orally administered, lipophilic, highly selective serotonin 5-HT(1B/1D) receptor agonist ('triptan') that is effective in the acute treatment of moderate to severe migraine attacks in adults [10].
• Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a comparative review [11].

Chemical compound and disease context of Triptan

• Eletriptan is therefore a useful addition to the triptan family and a first-line treatment option in the acute management of migraine attacks [10].
• It can be concluded that migraine patients who respond infrequently to sumatriptan should be switched to a different triptan, as lack of response to one triptan does not predict likelihood of responsiveness to another [12].
• Forty patients with migraine consecutively seen in our clinic were randomized to treat two consecutive moderate or severe attacks with one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two attacks with the same triptan and placebo, in counterbalanced order [13].
• Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral bioavailability than any other triptan, with more than two thirds of the administered dose absorbed within the first hour both inside and outside of a migraine attack [14].
• Naratriptan is a newly developed triptan shown to be effective in the treatment of migraine [15].

Biological context of Triptan

• This mechanism may underlie one of the anti-migraine actions of the triptan class exemplified by rizatriptan and suggests that the guinea-pig is an appropriate species in which to investigate the pharmacology of neurogenic dural vasodilation [16].
• The area under the curves (AUC) during 72 h of untreated attacks was compared with attacks treated with a triptan [17].
• Patients who had taken a triptan within 3 days prior to the investigation showed platelet activation values similar to the control group [18].
• In contrast, the increased 5-HT synthesis rate observed after chronic sumatriptan might possibly result from a down-regulation/desensitization of 5-HT1 receptors and/or unmasking of excitatory triptan-sensitive 5-HT receptors [19].
• OBJECTIVES: To investigate the demographic characteristics associated with triptan use, and examine the rate of co-prescription of triptans with specified pharmacologic agents with the potential for drug interactions [20].

Anatomical context of Triptan

• If treatment-emergent central nervous system (CNS) symptoms following triptan therapy represent direct pharmacological effects of the drug, they should occur independent of response to active drug [21].
• 5. The present results demonstrate that the triptan-induced contraction in brain vessels is mediated exclusively by the 5-HT1B receptor, which is also present in a majority of human coronary arteries [22].
• Anti-migraine triptan drugs block vasodilatation by binding to 5-HT1B/1D receptors localized on the peripheral sensory terminals and dural blood vessel smooth muscles [23].
• Chronic triptan treatment had no effect in two functional assays [sumatriptan mediated inhibition (50 mg/kg, i.p.) of electrically induced plasma protein extravasation in dura mater and 5-nonyloxytryptamine-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate binding in substantia nigra] [24].
• The present results demonstrate that triptan-induced contraction in guinea-pig iliac arteries is mediated by the 5-HT1B receptor [25].

Associations of Triptan with other chemical compounds

• Previous studies suggest that calcitonin gene-related peptide (CGRP) released from Adelta-fibres plays a more important role than substance P (SP) released from C-fibres in inducing dural vasodilatation and that one of the antimigraine mechanisms of triptan drugs is inhibiting CGRP release [23].
• PARTICIPANTS: The Triptan Cardiovascular Safety Expert Panel was composed of a multidisciplinary group of experts in neurology, primary care, cardiology, pharmacology, women's health, and epidemiology [26].
• CONCLUSIONS: Eletriptan 40 mg provides the best value in terms of the lowest DNT, assuming an approximately equal AWP discount for each triptan [27].

Gene context of Triptan

• Its ability to serve as a substrate for human P-glycoprotein (P-gp) was also investigated since a central mechanism of action has been proposed for this "triptan" class of drug [28].
• Neural 5-HT1D and/or 5-HT1F receptors localized pre-junctionally on trigeminovascular afferents appear to mediate the triptan-induced inhibition of the neurogenic inflammatory response, with possible additional sites of action for brain penetrant 5-HT1 receptor agonists in inhibiting the transmission of pain centrally [29].
• Acute treatment with a 5-HT(1B/1D) agonist (triptan) results in alleviation of the headache and normalization of the cranial venous CGRP levels, in part due to a presynaptic inhibitory effect on sensory nerves [30].
• These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo [31].
• Thus, adenoviral gene transfer can be used in trigeminal ganglia neurons for studying the mechanisms of triptan drug action on CGRP synthesis [32].

Analytical, diagnostic and therapeutic context of Triptan

• Triptan trials have similar designs, facilitating meta-analysis; this will provide a foundation for using triptans in clinical practice [33].
• Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization [8].
• Empirical findings based on clinical trials have led to associations between triptan pharmacology and efficacy [34].
• Controlled clinical trials and post-marketing surveillance studies were reviewed to document the incidence of chest symptoms after triptan therapy [35].
• Although the migraine clinical trials literature is enormous, we identified only nine published double-blind studies which compare an oral triptan with a non-triptan acute treatment [36].

References