Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. Five hundred eighty-six assessable patients received naratriptan 2.5 mg, 595 received 1 mg, 591 received 0.25 mg, 602 received placebo. Headache relief (moderate or severe pain reduced to mild or none) 4 hours postdose was reported in 68% of patients after treatment with naratriptan 2.5 mg compared with 57% after 1 mg, 39% after 0.25 mg, and 33% after placebo (p < 0.001 naratriptan 2.5 mg and 1 mg versus placebo and 1 mg and 2.5 mg versus 0.25 mg). 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. Naratriptan was also more effective than placebo in reducing clinical disability and the incidences of nausea, photophobia, and phonophobia. The overall incidence of adverse events and the incidences of specific adverse events did not differ in the naratriptan groups compared with placebo. No clinically relevant changes in ECG, blood pressure, or laboratory findings were reported. These data demonstrate that naratriptan is effective and well tolerated for the acute treatment of migraine. The 2.5-mg dose was associated with superior efficacy, whereas its adverse event profile was similar to that of placebo.
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PMID:Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, crossover study. The Naratriptan S2WA3003 Study Group. 1021 71

Naratriptan is a selective 5-HT(1B/1D) receptor agonist, with a high affinity at the 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptor subtypes. Naratriptan contracts a number of large isolated cerebral arteries from several species, and has little contractile effect on peripheral blood vessels. It has an inhibitory effect on the cranial neurogenic inflammation model. The clinically recommended dose is 2.5 mg. It was found significantly superior to placebo on headache relief and pain free at 2 and 4 hours, and in relieving nausea, photophobia and phonophobia. It also has a good within-patient consistency, and a low recurrence rate. The side-effect profile is that of the triptan class, wih an incidence no different from placebo at the 25 mg dose. The contraindications are similar to any triptan, including coronary disease. Naratriptan is unlikely to affect metabolism of other drugs. In comparison sumatriptan 100 mg, naratriptan 2.5 mg has a slower onset of action and a lower response rate at 4 h, but it has a lower recurrence rate, and is better tolerated.
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PMID:Naratriptan. 1246 78

The basic CNS neuropharmacology of naratriptan is reviewed here. Naratriptan is a second-generation triptan antimigraine drug, developed at a time when CNS activity was thought not to be relevant to its therapeutic effect in migraine. It was, however, developed to be a more lipid-soluble, more readily absorbed and less readily metabolized variant on preexisting triptans and these variations conferred on it a higher CNS profile. Naratriptan is a 5-HT(1B/1D) receptor agonist with a highly selective action on migraine pain and nausea, without significant effect on other pain or even other trigeminal pain. Probable sites of therapeutic action of naratriptan include any or all of: the cranial vasculature; the peripheral terminations of trigeminovascular sensory nerves; the first-order synapses of the trigeminovascular sensory system; the descending pain control system; and the nuclei of the thalamus. Naratriptan may prevent painful dilatation of intracranial vessels or reverse such painful dilatation. Naratriptan can prevent the release of sensory peptides and inhibit painful neurogenic vasodilatation of intracranial blood vessels. At the first order synapse of the trigeminal sensory system, naratriptan can selectively suppress neurotransmission from sensory fibers from dural and vascular tissue, while sparing transmission from other trigeminal fibers, probably through inhibition of neuropeptide transmitter release. In the periaqueductal gray matter and in the nucleus raphe magnus, naratriptan selectively activates inhibitory neurons which project to the trigeminal nucleus and spinal cord and which exert inhibitory influences on trigeminovascular sensory input. Naratriptan has also a therapeutic effect on the nausea of migraine, possibly exerting its action at the level of the nucleus tractus solitarius via the same mechanisms by which it inhibits trigeminovascular nociceptive input. The incidence of naratriptan-induced adverse effects in the CNS is low and it is not an analgesic for pain other than that of vascular headache. In patients receiving selective serotonin uptake inhibitors (SSRIs) naratriptan may cause serotonin syndrome-like behavioral side effects. The mechanism of action involved in the production of behavioral and other CNS side effects of naratriptan is unknown.
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PMID:Preclinical neuropharmacology of naratriptan. 1638 95