Disease relevance of C07792

• Naratriptan is effective and well tolerated in the acute treatment of migraine [1].
• CONCLUSIONS: These results show that at therapeutic doses, naratriptan exerts only a minor effect on myocardial blood flow, coronary vasodilator reserve, or coronary resistance among subjects with no evidence of ischemic heart disease [2].
• Naratriptan was also more effective than placebo in reducing clinical disability and the incidences of nausea, photophobia, and phonophobia [3].
• Meningitis caused a depletion of calcitonin gene-related peptide (CGRP) and substance P from meningeal nerve fibers, which was prevented by zolmitriptan and naratriptan [4].
• Naratriptan prophylactic treatment in cluster headache [5].

High impact information on C07792

• The 5-HT(1B/1D) agonist, naratriptan, was microinjected into the ventrolateral periaqueductal gray (vlPAG), and activity in the trigeminal nucleus caudalis (TNC) was monitored [6].
• Naratriptan decreased the excitability to electrical stimulation of the dura mater as the A-fiber response decreased by 24 +/- 4.1% (p < 0.001) and the C-fiber response decreased by 42 +/- 8.2% (p < 0.001) [6].
• The selective 5HT1B/1D agonist naratriptan has no significant activity at 5HT2 receptors; however, like all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary arteries by activation of 5HT1B receptors [2].
• For example, bioavailability of oral formulations ranges between 14% (sumatriptan) and 74% (naratriptan), and their elimination half-life ranges from 2 hours (sumatriptan and rizatriptan) to 25 hours (frovatriptan) [7].
• Modulation of neuronal activity in the nucleus raphé magnus by the 5-HT(1)-receptor agonist naratriptan in rat [8].

Chemical compound and disease context of C07792

• This paper describes the aggregation, validation and initial analysis of data from the sumatriptan/naratriptan aggregate patient (SNAP) database, which to date comprises pooled individual-patient data from 128 clinical trials conducted from 1987 to 1998 with the migraine medications sumatriptan and naratriptan [9].
• Patients (n = 548) meeting International Headache Society (IHS) criteria for migraine were randomized to treat a single migraine attack with either eletriptan 40 mg, naratriptan 2.5 mg, or placebo [10].
• We describe the preventive use of naratriptan, mostly as add-on to high-dose verapamil treatment, in nine patients with cluster headache [11].
• The combination of naratriptan and prochlorperazine in migraine treatment [12].
• METHODS: In a double-blind, double-dummy, crossover study, 12 patients with migraine treated 2 migraine attacks with the nonspecific antimigraine drug, naproxen (500-mg capsule) or the more specific antimigraine drug, naratriptan (2.5-mg tablet) [13].

Biological context of C07792

• In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD50 dose = 19 +/- 3 micrograms kg-1) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID50 = 4.1 micrograms kg-1) [14].
• Uncertainty analysis in pharmacokinetics and pharmacodynamics: application to naratriptan [15].
• Subjects were given either 2.5 mg naratriptan or placebo to treat a single MRM episode, defined as starting between days -2 and +4 relative to the start of menstruation [16].
• Preclinical neuropharmacology of naratriptan [17].
• Naratriptan can prevent the release of sensory peptides and inhibit painful neurogenic vasodilatation of intracranial blood vessels [17].

Anatomical context of C07792

• Naratriptan, CP122638, and dihydroergotamine stimulated [35S]GTPgammaS binding to a similar level as L694247 in hippocampus, lateral septum, and dorsal raphe [18].
• In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord [19].
• Agonist-directed trafficking explaining the difference between response pattern of naratriptan and sumatriptan in rabbit common carotid artery [20].
• Naratriptan has high affinity for human recombinant 5HT1B and 5HT1D receptors (pKi = 8.7 +/- 0.03 and 8.3 +/- 0.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC50 values of 0.11 and 0.07 microM, respectively) [14].
• The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat [21].

Associations of C07792 with other chemical compounds

• 4. 2'-Methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-e-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127,935), methiothepin and ketanserin each behaved as silent, competitive antagonists at rb 5HT1B receptors; pKB values were 8.41, 8.32 and 7.05, respectively when naratriptan was used as an agonist [22].
• Frovatriptan, zolmitriptan, rizatriptan, naratriptan, sumatriptan, and almotriptan contracted guinea-pig iliac arteries with pD2 values of 7.52+/-0.04, 6.72+/-0.03, 6.38+/-0.06, 6.22+/-0.05, 5.86+/-0.05 and 5.26+/-0.04 respectively [23].
• Eletriptan pharmacology has also been evaluated in vitro in comparison with zolmitriptan (AstraZeneca plc) and naratriptan (GlaxoSmithKline plc) [290116] [24].

Gene context of C07792

• L 694247 appears to possess higher efficacy at 5-HT1A receptors compared with 8-OH-DPAT and naratriptan [25].
• Unlike ketanserin, GR 127,935 potently antagonised the naratriptan response in C6-glial/5-HT1B cells while also depressing the maximum response [26].
• Differential effects of the 5HT1B/1D receptor agonist naratriptan on trigeminal versus spinal nociceptive responses [19].
• The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphonamide), a novel 5HT1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine [14].
• Naratriptan causes small contractions of human isolated coronary arteries (EC50 value of 0.17 microM; maximum contraction equivalent to 33% of 5HT maximum) [14].

Analytical, diagnostic and therapeutic context of C07792

• Headache relief was maintained 8, 12, and 24 hours postdose with no use of rescue medication or a second dose of study medication by significantly (p < 0.001) greater percentages of patients after treatment with naratriptan 2.5 mg or 1 mg compared with naratriptan 0.25 mg or placebo [3].
• The efficacy and tolerability of naratriptan tablets (2.5 mg, 1 mg, and 0.25 mg) compared with placebo in the acute treatment of migraine were evaluated in a randomized, double-blind, four-period crossover study [3].
• We conducted this series of experiments to further elucidate the site of action of naratriptan using a well-established animal model of trigeminovascular stimulation [27].
• Cardiac haemodynamics and coronary artery diameter were measured at baseline and after subcutaneous injections of placebo and naratriptan (1.5 mg, s.c.) in 10 patients undergoing diagnostic cardiac catheterisation [28].
• Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials [29].

References