Neuropharmacology
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Triptans share the pharmacological profile of being 5-hydroxytryptamine (5-HT1B/1D) agonists and having potent anti-migraine activity. The conformationally restricted zolmitriptan analogue 4991W93 was developed as a potent, and at low doses, specific, non-vasconstrictor inhibitor of neurogenic dural plasma protein extravasation. Here, we sought to study the effect of 4991W93 at plasma protein extravasation blocking and at 5-HT(1B/1D) agonist doses. ⋯ When applied iontophoretically, 4991W93 did not appear to have an additive effect over a 5-HT(1B/1D) agonist effective concentration of zolmitriptan. These data suggest that 4991W93 is only effective at modulating the trigeminocervical complex at 5-HT(1B/1D) agonist doses. To account for neurogenic dural plasma protein extravasation blockade in animal studies, 4991W93 might have non-5-HT(1B/1D)-based pharmacological targets that are yet to be described.