5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism

被引：14

作者：

Leth-Petersen, Sebastian ^{[1
]}

Petersen, Ida N. ^{[1
]}

Jensen, Anders A. ^{[1
]}

Bundgaard, Christoffer ^{[2
,3
]}

Baek, Mathias ^{[1
]}

Kehler, Jan ^{[2
,3
]}

Kristensen, Jesper L. ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen O, Denmark

[2] H Lundbeck & Co AS, Dept Discovery Chem, Ottiliavej 9, DK-2500 Valby, Denmark

[3] H Lundbeck & Co AS, DMPK, Ottiliavej 9, DK-2500 Valby, Denmark

来源：

ACS CHEMICAL NEUROSCIENCE | 2016年 / 7卷 / 11期

关键词：

Phenethylamines; hallucinogens; microsomal stability; 5-HT2A receptor agonists; AGONIST LIGANDS; 5-HT2A; BINDING;

D O I：

10.1021/acschemneuro.6b00265

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 S-HT2A/5-HT2C receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT2 receptor agonist properties, all analogues had an intrinsic clearance above 1.3 L/kg/h predictive of high first-pass metabolism.

引用

页码：1614 / 1619

页数：6

共 50 条

[1] Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors
Eshleman, Amy J.
Wolfrum, Katherine M.
Reed, John F.
Kim, Sunyoung O.
Johnson, Robert A.
Janowsky, Aaron
BIOCHEMICAL PHARMACOLOGY, 2018, 158 : 27 - 34
[2] Synthesis and in vitro pharmacological evaluation of a new series of 5-HT1A 5-HT2A and 5-HT2C receptor ligands containing a norbornene nucleus
Fiorino, F.
Severino, B.
De Angelis, F.
Perissutti, E.
Magli, E.
Frecentese, F.
Esposito, A.
Massarelli, P.
Nencini, C.
Viti, B.
Santagada, V.
Caliendo, G.
PHARMAZIE, 2009, 64 (09): : 555 - 564
[3] The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice
Carbonaro, Theresa M.
Eshleman, Amy J.
Forster, Michael J.
Cheng, Kejun
Rice, Kenner C.
Gatch, Michael B.
PSYCHOPHARMACOLOGY, 2015, 232 (01) : 275 - 284
[4] Mechanism of tolerance development to 2,5-dimethoxy-4-iodoamphetamine in rats:: down-regulation of the 5-HT2A, but not 5-HT2C, receptor
Smith, RL
Barrett, RJ
Sanders-Bush, E
PSYCHOPHARMACOLOGY, 1999, 144 (03) : 248 - 254
[5] Mechanism of tolerance development to 2,5-dimethoxy-4-iodoamphetamine in rats: down-regulation of the 5-HT2A, but not 5-HT2C, receptor
R. L. Smith
Robert J. Barrett
Elaine Sanders-Bush
Psychopharmacology, 1999, 144 : 248 - 254
[6] ROLE OF 5-HT2A AND 5-HT2C RECEPTORS IN THE STIMULUS EFFECTS OF HALLUCINOGENIC DRUGS .2. REASSESSMENT OF LSD FALSE POSITIVES
FIORELLA, D
RABIN, RA
WINTER, JC
PSYCHOPHARMACOLOGY, 1995, 121 (03) : 357 - 363
[7] The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice
Theresa M. Carbonaro
Amy J. Eshleman
Michael J. Forster
Kejun Cheng
Kenner C. Rice
Michael B. Gatch
Psychopharmacology, 2015, 232 : 275 - 284
[8] Synthesis and 5-HT2A radioligand receptor binding assays of DOMCI and DOMOM, two novel 5-HT2A receptor ligands
Harms, A
Ulmer, E
Kovar, KA
ARCHIV DER PHARMAZIE, 2003, 336 (03) : 155 - 158
[9] Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response
Erkizia-Santamaria, I
Alles-Pascual, R.
Horrillo, I
Meana, J. J.
Ortega, J. E.
BIOMEDICINE & PHARMACOTHERAPY, 2022, 154
[10] Antagonist Functional Selectivity: 5-HT2A Serotonin Receptor Antagonists Differentially Regulate 5-HT2A Receptor Protein Level In Vivo
Yadav, Prem N.
Kroeze, Wesley K.
Farrell, Martilias S.
Roth, Bryan L.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2011, 339 (01) : 99 - 105

← 1 2 3 4 5 →