The potentially beneficial central nervous system activity profile of ivacaftor and its metabolites.

ABSTRACT: Ivacaftor-lumacaftor and ivacaftor are two new breakthrough cystic fibrosis transmembrane conductance modulators. The interactions of ivacaftor and its two metabolites hydroxymethylivacaftor (iva-M1) and ivacaftorcarboxylate (iva-M6) with neurotransmitter receptors were investigated in radioligand binding assays. Ivacaftor displayed significant affinity to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT_2C receptor (pK_i=6.06±0.03), β₃-adrenergic receptor (pK_i=5.71±0.07), δ-opioid receptor (pK_i=5.59±0.06) and the dopamine transporter (pK_i=5.50±0.20); iva-M1 displayed significant affinity to the 5-HT_2C receptor (pK_i=5.81±0.04) and the muscarinic M3 receptor (pK

SUBMITTER: Schneider EK 

PROVIDER: S-EPMC5850045 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature