Figures
- FIGURE 1
a) Secondary binding data for ivacaftor. [3H]mesulergine displacement data (Ki=866 nM) binding to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT2C receptor. The reference compound is ritanserin (Ki=0.57 nM). b) Secondary binding data for ivacaftorcarboxylate (iva-M6). [3H]ketanserin displacement data (Ki=147 nM) binding to the 5-HT2A receptor. The reference compound is clozapine (Ki=2.4 nM). CPM: counts per minute.
- FIGURE 2
Molecular docking models of a) ivacaftor bound to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT2C receptor and b) ivacaftorcarboxylate (iva-M6) bound to the 5-HT2A receptor. Ivacaftor, iva-M6 and residues within the receptor cavity are shown in ball-and-stick representation. The 5-HT2C and 5-HT2A receptors are shown in cartoon ribbon representation. The labelled side chains within the binding cavity represent contacts within 4 Å of the docked molecules.
- FIGURE 3
Results of the murine forced swim test and spontaneous locomotor activity tests for ivacaftor, fluoxetine and ketamine. a) Schematic diagram depicting the forced swim test. b) Effect of ivacaftor treatment (40 mg·kg−1 i.p. for 21 days) on swimming and climbing in the forced swim test (n=10). Fluoxetine (10.2 mg·kg−1 i.p. for 21 days) and ketamine (10 mg·kg−1 s.c.) were used as the comparators. c) Effect of ivacaftor, fluoxetine and ketamine on immobility in the forced swim test (n=10). *: p<0.05. d) Effect of ivacaftor and fluoxetine on spontaneous locomotor activity in the open field test measuring the distance (cm) travelled for 10 min (n=10). e) Effect of ivacaftor, fluoxetine and ketamine on spontaneous locomotor activity in the open field test measuring the number of touches for 10 min (n=10).
- FIGURE 4
Results of the AweScoreCF questionnaire completed by 23 adult cystic fibrosis (CF) patients 1 month before and 3 months after initiating ivacaftor–lumacaftor therapy: a) clinical parameters, b) general well-being, c) physical fitness, d) physique, e) psychological parameters and f) total score. Data are presented as mean±sem of a paired t-test. *: p<0.05. In eight out of 10 subdomains changes resulted in statistically significant improvement of quality of life and well-being of the 23 adult CF patients; a positive trend was observed in the subdomains sputum and mood.
Supplementary Materials
Supplementary Material
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Supplementary information 00127-2017_Supplementary_Information
Supplementary figures 00127-2017_Supplementary_Figures
