ACT-462206

ACT-462206 is a dual orexin receptor antagonist (IC50 for OX1 = 60nM, OX2 = 11nM) which has been investigated for the treatment of insomnia. In human trials, ACT-462206 produced dose-dependent sedative effects and was generally well tolerated, with residual sleepiness and headache being the most common adverse events.[1]

ACT-462206
Clinical data
Routes of
administration		Oral
Drug classOrexin receptor antagonist
Legal status
Legal status
  • Investigational
Identifiers
  • (2S)-N-(3,5-Dimethylphenyl)-1-[(4-methoxyphenyl)sulfonyl]-2-pyrrolidinecarboxamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC20H24N2O4S
Molar mass388.48 g·mol−1
3D model (JSmol)
  • O=C(NC=1C=C(C=C(C1)C)C)C2N(CCC2)S(=O)(=O)C3=CC=C(OC)C=C3
  • InChI=InChI=1S/C20H24N2O4S/c1-14-11-15(2)13-16(12-14)21-20(23)19-5-4-10-22(19)27(24,25)18-8-6-17(26-3)7-9-18/h6-9,11-13,19H,4-5,10H2,1-3H3,(H,21,23)/t19-/m0/s1
  • Key:NHPQGZOBHSVTAQ-IBGZPJMESA-N

Pharmacology

In humans, the sedative effects of ACT-462206 began 45 minutes after oral administration, and dissipated within 8 hours - consistent with a favorable pharmacodynamic profile for the treatment of insomnia. However, the pharmacokinetic profile of ACT-462206 diverges significantly from what would be expected based on behavioral effects. Elevated plasma concentrations of ACT-462206 are sustained for over 24–36 hours after administration - despite behavioral measures of sedation disappearing within 8 hours of administration.[1]

References
  1. Hoch M, van Gorsel H, van Gerven J, Dingemanse J (September 2014). "Entry-into-humans study with ACT-462206, a novel dual orexin receptor antagonist, comparing its pharmacodynamics with almorexant". Journal of Clinical Pharmacology. 54 (9): 979–986. doi:10.1002/jcph.297. PMID 24691844. S2CID 40714628.


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