title: 5-HT2A/5-HT2CReceptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism.
abstract: The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and 5-HT2A/5-HT2Creceptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT2receptor agonist properties, all analogues had an intrinsic clearance above 1.3 L/kg/h predictive of high first-pass metabolism.
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 København Ø, Denmark.
authors: Sebastian
authors: S
authors: Leth-Petersen
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 København Ø, Denmark.
authors: Ida N
authors: IN
authors: Petersen
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 København Ø, Denmark.
authors: Anders A
authors: AA
authors: Jensen
authors: Department of Discovery Chemistry and DMPK, H. Lundbeck A/S , Ottiliavej 9, 2500 Valby, Denmark.
authors: Christoffer
authors: C
authors: Bundgaard
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 København Ø, Denmark.
authors: Mathias
authors: M
authors: Bæk
authors: Department of Discovery Chemistry and DMPK, H. Lundbeck A/S , Ottiliavej 9, 2500 Valby, Denmark.
authors: Jan
authors: J
authors: Kehler
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 København Ø, Denmark.
authors: Jesper L
authors: JL
authors: Kristensen
mesh_terms: D000840:Anisoles / Q000737:chemistry; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D057809:HEK293 Cells; D006213:Hallucinogens / Q000737:chemistry; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010627:Phenethylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000840:Anisoles; D006213:Hallucinogens; D010627:Phenethylamines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; C000595926:2-(4-bromo-2,5-dimethoxyphenyl)-N-((2-methoxyphenyl)methyl)ethanamine
keywords: 5-HT2A receptor agonists; Phenethylamines; hallucinogens; microsomal stability