Naratriptan (hydrochloride)

Naratriptan (GR-85548A) hydrochloride is a selective 5-HT1B/1D receptor agonist. Naratriptan hydrochloride is peripherally active and has good oral bioavailability, inducing cranial artery vasoconstriction by activating 5-HT1B/1D receptors (EC₅₀=0.11 μM for dog basilar artery). Naratriptan hydrochloride also inhibits trigeminal nerve-mediated dural neurogenic plasma extravasation and reduces sterile inflammation. Naratriptan hydrochloride is mainly used in the research of acute migraine, targeting cranial vascular and neuroinflammatory mechanisms^[1][2][3][4]. In Vitro:Naratriptan hydrochloride targets human recombinant 5-HT1B and 5-HT1D receptors with K_i of 0.47 nM and 0.69 nM, and EC₅₀ of 4.4 nM and 23 nM, respectively; while for 5-HT1A, K_i=26 nM, EC₅₀=79 nM^[1].
Naratriptan hydrochloride targets 5-HT1B, 5-HT1D, and 5-HT1F with pK_i of 8.7, 8.3, and 8.1, respectively^[2].
Naratriptan hydrochloride can inhibit the discharge response of cat-derived nucleus tractus solitarius (NTS) cells that regulate vomiting by 54%; this activity suggests that Naratriptan hydrochloride has inhibitory activity on NTS in trigeminal nerve vessels and can be used in the study of migraine inhibition^[2].
Naratriptan hydrochloride induces concentration-dependent contraction in isolated dog basilar artery and middle cerebral artery experiments, with EC₅₀ of 0.11 M and 0.07 M, respectively^[3].
Naratriptan hydrochloride induces contraction in isolated human epicardial coronary arteries with an EC₅₀ value of 0.17 μM; the maximal contraction induced at this point is 33% of the maximal 5-HT response^[3].
In Vivo:Naratriptan (0.1-10 μg/kg; intravenous cannulation; single dose; 15 min before electrical stimulation of the trigeminal ganglion) hydrochloride inhibits plasma protein extravasation in the rat dural neurogenic inflammation model with an ID₅₀ of 4.1 μg/kg^[3].
Naratriptan (10 mg/kg; oral; single dose) hydrochloride has an oral bioavailability of 71% in male Wistar rats. Naratriptan (0.5 mg/kg; oral; single dose) hydrochloride has an oral bioavailability of 95% in beagle dogs^[3].
Contrary to the activity of μ-opioid receptor agonists, Naratriptan [(10, 30 μg/kg; intrathecal injection; single dose) or (10, 30 mg/kg; subcutaneous injection; single dose)] hydrochloride does not increase the latency of the tail flick response or hot plate response in mice in the tail flick test or hot plate test. Neither or Naratriptan (10, 30 mg/kg; subcutaneous injection; single dose) hydrochloride also does not increase the nociceptive paw pressure threshold in the paw pressure test in guinea pigs and rats^[3].
Naratriptan (10 mg/mL; IV/iontophoresis; single dose) hydrochloride inhibits the responses of trigeminal nucleus caudalis neurons to sagittal sinus stimulation in the cat trigeminal neurovascular stimulation model, an effect that can be reversed by the 5-HT_1B/1D receptor antagonists (5 mg/mL) SB224289 (HY-101105) and BRL15572 (HY-13200B)^[4].