Disease relevance of Alniditan

• Both of these suggestions warrant further and larger trials of alniditan in acute migraine [1].
• Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability [1].
• Alniditan produced a slight bradycardia (maximum change: -4 +/- 1%) and a more pronounced hypotensive effect (maximum change: -23 +/- 5%) [2].
• Iontophoresis slightly increased drug quantities in stratum corneum compared to passive diffusion but it strongly increased alniditan quantities in viable skin. ii) The objective to deliver in vivo 0.5 mg of alniditan within less than 1 h was reached but an erythema was detected at the anode [3].
• In six animals pre-treated with the potent and selective 5-HT1B/1D receptor antagonist, GR127935, the alniditan-induced changes in carotid haemodynamics were clearly antagonised, whereas the bradycardia and hypotension remained unaffected [2].

High impact information on Alniditan

• Therefore, in functional assays, the potency of alniditan was much higher at 5-HT1D receptors than at 5-HT1A receptors [4].
• We investigated the receptor-binding profile in vitro of alniditan compared with sumatriptan and dihydroergotamine for 28 neurotransmitter receptor subtypes, several receptors for peptides and lipid-derived factors, ion channel-binding sites, and monoamine transporters [4].
• Alniditan revealed nanomolar affinity for calf substantia nigra 5-HT1D and for cloned h5-HT1D alpha, h5-HT1D beta and h5-HT1A receptors (Ki = 0.8, 0.4, 1.1, and 3.8 nM, respectively) [4].
• In signal transduction assays using cells expressing recombinant h5-HT1D alpha, h5-HT1D beta, or h5-HT1A receptors, alniditan (like 5-HT) was a full agonist for inhibition of stimulated adenylyl cyclase (IC50 = 1.1, 1.3, and 74 nM, respectively, for alniditan) [4].
• Second, the novel 5-HT1B/D agonists zolmitriptan (311C90), rizatriptan (MK-462), eletriptan (UK-116,044), avitriptan (BMS-180048) and alniditan (R091274) were all proved superior to placebo for attack treatment, but their advantages over sumatriptan are yet to be analysed in more detail [5].

Biological context of Alniditan

• A higher lipophilicity explains (except for alniditan) their greater oral bioavailability and better central nervous system penetration [5].
• Selective vasoconstriction by alniditan in the carotid vascular bed of anaesthetized dogs [6].

Anatomical context of Alniditan

• The antimigraine agent alniditan selectively constricts porcine carotid arteriovenous anastomoses via 5-HT1B/1D receptors [2].
• Effects of alniditan on neurogenic oedema in the rat dura mater and on contraction of rat basilar artery [7].

Gene context of Alniditan

• 1. Alniditan, a novel migraine abortive agent, is a potent 5-HT1B/5-HT1D receptor agonist of nM affinity [8].

Analytical, diagnostic and therapeutic context of Alniditan

• The mechanism of alniditan permeation by iontophoresis was investigated [3].
• The aim of this study was to evaluate the transdermal permeation of alniditan by electroporation and to compare with iontophoretic delivery [9].

References