The affinity of triptans


Application note

Analyzing In Vitro Results for the 5-HT Ligands

The affinity of triptans for 5-ht subtypes

The key reference drugs of the 5-HT1B/D agonist sub-family of the triptans are almotriptan, naratriptan, rizatriptan and sumatriptan. The full activity profile for these drugs is visualized in a Heatmap (Figure 2). Extensive data are available on sumatriptan and the Heatmap clearly displays the selectivity profile of that drug.

Full affinity/activity profile for sumatriptan, rizatriptan, naratriptan and almotriptan | Elsevier
Figure 2. The Heatmap showing the full affinity/activity profile for sumatriptan, rizatriptan, naratriptan and almotriptan (in order of appearance down the left hand column)

The pX values for almotriptan, naratriptan, rizatriptan and sumatriptan for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT6 and 5-HT7 were selected using Analysis View and viewed as a Heatmap (Figure 3).

A

Analysis assessing the Polypharmacology of 1,4-Benzodiazepines | Industry Insights

B

The biological screening results for the 39 compounds on Cav3.2 channels | R&D Solutions
Figure 3. A. Analysis View was used to filter the Heatmap by target. B. The Heatmap showing the affinity/activity profile (pX values) for selected 5-HT subtypes for sumatriptan, rizatriptan, naratriptan and almotriptan (in order of appearance down the left hand column).

A large number of binding data points are available for naratriptan, rizatriptan and particularly for sumatriptan against all of the targets selected, especially the 5-HT1B and 5-HT1D receptors (Figure 4). pX values extracted from the literature show a large variation, especially for sumatriptan against the 5-HT1B and 5-HT1D receptors.

Analyzing In Vitro Results for the 5-HT Ligands - Industry Insights | R&D Solutions
Figure 4. Binding affinities of the selected triptans against the 5-HT subtypes. Each binding point represents a pX value extracted from publications or patents.

The large number of data points available for sumatriptan on 5-HT1B resulted in significant differences in reported pX values. Differences in the experimental conditions under which these data were obtained could explain the discrepancies. Figure 5 illustrates the analysis of these data points by receptor species and by human cell line used in the assay.

Analyzing In Vitro Results for the 5-HT Ligands - Industry Insights | R&D Solutions
Human binding data by Cell Line - Industry Insights | Elsevier R&D Solutions
Figure 5. Binding affinities, expressed in pX values, of sumatriptan for 5-HT1Bsubtypes. The top chart displays the affinities according to the different target protein species. The bottom chart shows how the human binding data is spread out depending on the cell line used.