Migraine, a debilitating neurological disorder, affects millions worldwide. However, current treatments often fall short in efficacy and tolerability. This brings us to calcitonin gene-related peptide receptors (CGRP receptors) – promising targets in migraine management. In addition, CGRPs are neuropeptides that play crucial roles in pain transmission and vasodilation, which are key features of migraines. Therefore, Telcagepant, an orally active CGRP receptor antagonist, is an potent anti-acute migraine agent. Telcagepant acts against the relaxation induced by CGRP, while leaving vascular tone unaffected. This ability to inhibit CGRP’s vasodilatory effects peripherally underscores Telcagepant’s potential to alleviate migraine-associated symptoms, including headaches, without triggering unwanted coronary side effects.

Telcagepant is an orally active CGRP receptor antagonist for acute migraine research.

In vitro, Telcagepant exhibits affinity (Ki) for both canine and rat receptors, recording values of 1204 nM and 1192 nM respectively. Furthermore, it effectively blocks human α-CGRP-stimulated cAMP responses in HEK293 cells expressing the human CGRP receptor, with an IC50 as low as 2.2 nM. In addition to this, Telcagepant (MK-0974) shows saturable binding to SK-N-MC membranes with a KD of 1.9 nM. Likewise, it demonstrates saturable binding to rhesus cerebellum homogenate with a KD of 1.3 nM. Telcagepant also inhibits CGRP receptor activity in vascular smooth muscle cultures from global hRAMP1 mice (IC50: 0.16 μM).

In preclinical animal models, Telcagepant, when administered intravenously at a 1 mg/kg bolus, shows that its efficacy is time-dependent and linked with plasma levels. It exhibits linear pharmacokinetics across a range of 0.5-10 mg/kg when delivered intravenously to monkeys.

In conclusion, Telcagepant is an orally active CGRP receptor antagonist. And Telcagepant represents hope for migraine sufferers with its novel action mechanism and promising experimental outcomes. More extensive clinical trials will add further insights into this exciting medication prospect.


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