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| Trade names | Amerge, Naramig, others |
| Other names | GR-85548; GR85548; GR-85548A; GR85548A; SMP-948; SMP948 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601083 |
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| Routes of administration | Oral |
| Drug class | Serotonin5-HT1B,5-HT1D,5-HT1E, and5-HT1F receptoragonist;Antimigraine agent;Triptan |
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| Pharmacokinetic data | |
| Bioavailability | 74% |
| Metabolism | Hepatic |
| Eliminationhalf-life | 5–8 hours |
| Excretion | Renal |
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| ECHA InfoCard | 100.121.501 |
| Chemical and physical data | |
| Formula | C17H25N3O2S |
| Molar mass | 335.47 g·mol−1 |
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Naratriptan, sold under the brand namesAmerge andNaramig among others, is atriptandrug marketed byGlaxoSmithKline and is used for the treatment ofmigraineheadaches. It is aselectiveserotonin5-HT1 receptor familyagonist.
It was patented in 1987 and approved for medical use in 1997.[1]
Naratriptan is used for the treatment of the acute migraine attacks and the symptoms of migraine, including severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound or light.[2]
A meta-analysis of 53 clinical trials has shown that all triptans are effective for treating migraine at marketed doses and that naratriptan, although less effective thansumatriptan andrizatriptan was more effective than placebo in reducing migraine symptoms at two hours[3] and efficacy was demonstrated in almost two thirds of subjects after four hours of treatment.[4]
Side effects are similar to other triptan medications, with the incidence of side effects reportedly being lower than sumatriptan, and side effects occurring rarely except when above 2.5mg.[5][6] The risk of triptan side effects is also in general low, according to a systematic review.[7] Side effects include: sensations of warmth/heat, dizziness,drowsiness,tingling of the hands or feet, nausea,dry mouth and unsteadiness, chest pain/pressure, throat pain/pressure, unusually fast/slow/irregular pulse, and mental/mood changes.[6] The tingling and heaviness and sensation of warmth/heat is characteristic of selective5-HT1 agonists.[6]
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 15–79 (Ki) 302–>10,000 (EC50Tooltip half-maximal effective concentration) 65–79% (EmaxTooltip maximal efficacy) |
| 5-HT1B | 0.47–9.4 (Ki) 1.4–25 (EC50) 80–98% (Emax) |
| 5-HT1D | 0.50–5.0 (Ki) 0.91–4.4 (EC50) 67–103% (Emax) |
| 5-HT1E | 7.4–20 (Ki) 6.8–31 (EC50) 97% (Emax) |
| 5-HT1F | 1.8–43 (Ki) 4.2–367 (EC50) 98% (Emax) |
| 5-HT2A | >10,000 (Ki) >10,000 (EC50) |
| 5-HT2B | 8,320 (Ki) >10,000 (EC50) |
| 5-HT2C | >3,160 (Ki) ND (EC50) |
| 5-HT3 | >3,160 (mouse) |
| 5-HT4 | >3,160 (guinea pig) |
| 5-HT5A | 3,390 (rat) |
| 5-HT6 | >3,160 |
| 5-HT7 | 1,170–>3,160 (Ki) >10,000 (EC50) |
| α1A–α1D | ND |
| α2A–α2C | ND |
| β1–β3 | ND |
| D1–D5 | ND |
| H1–H4 | ND |
| M1–M5 | ND |
| I1,I2 | ND |
| σ1,σ2 | ND |
| TAAR1Tooltip Trace amine-associated receptor 1 | ND |
| SERTTooltip Serotonin transporter | ND |
| NETTooltip Norepinephrine transporter | ND |
| DATTooltip Dopamine transporter | ND |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified.Refs:[8][9][10][11][12][13][14][15] [16][17][18][19][20][21][22][23] | |
The causes of migraine are not clearly understood; however, the efficacy of naratriptans and other triptans is believed to be due to their activity as5-HT (serotonin) agonists. The biological and pharmacokinetic profile of naratriptan differs significantly from sumatriptan.[6]
Naratriptan is atriptan and amodifiedanalogue oftryptamines like thepsychedelic drugdimethyltryptamine (DMT).[24] However, naratriptan itself is not technically a tryptamine as it features a (1-methylpiperidin-4-yl)side chain instead of theethylamine side chain present in tryptamines.[24] Besides this difference, naratriptan is substituted at the 5 position of theindolering system and theaminemoiety has beencyclized.[24] Instead of being a tryptamine, naratriptan is apiperidinylindole.[24]
The experimentallog P of naratriptan is 1.6 to 2.16 and its predicted log P is 0.28 to 2.16.[25][24][26]
Naratriptan waspatented in 1987 and was introduced for medical use in 1997.[1]
In the United States, theFood and Drug Administration (FDA) approved naratriptan on February 11, 1998.[27] It was covered byU.S. Patent no. 4997841; the FDA lists the patent as expiring on July 7, 2010.[27][28]
In July 2010, in the wake of the patent expiration, several drug manufacturers, includingRoxane Labs,[29]Sandoz[30] andTeva Pharmaceuticals,[31] announced that they were launching generic Naratriptan medications.
The drug continued to be covered by European patent 0303507 in Germany, Spain, France and the United Kingdom through March 10, 2012,[32] and by Australian patent 611469 in Australia through June 17, 2013.[32] It had previously been covered by Canadian patent 1210968; but both Sandoz and Teva (formerly Novopharm) have offered generic equivalents in Canada since that patent's expiration December 1, 2009.[32]
On December 23, 2014, in response to a request fromHealth Canada, importers in Canada agreed toquarantine the importation of health products, including generic Naratriptan manufactured for both Sandoz and Teva, fromDr. Reddy's Laboratories inSrikakulam,India.[33][34] Because Teva and Sandoz are the only approved suppliers of generic Naratriptan in Canada, the quarantine resulted in Naratriptan being placed on the Canadian drug shortage list.[35]
Following the Canadian quarantine, theUnited Arab Emirates'Ministry of Health also imposed a similar quarantine.[35][36]
Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]
Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]
TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]
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