Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies

Journal of Psychopharmacology
Hiba SalihPeter De Boer

Abstract

Metabotropic glutamate receptor-2 positive allosteric modulator, JNJ-40411813 (ADX71149), was characterised for clinical effects in healthy volunteers in two phase-1 studies. In study 1, healthy men received 50-, 100-, 150- or 225 mg and women received 100 mg JNJ-40411813 (n=6, each cohort) or placebo (n=2, each cohort) twice daily for seven days; smoking men (n=30) received placebo twice daily on days 1-7, 100 mg JNJ-40411813 (n=20) or placebo (n=10) on days 8-14. In study 2, healthy men received intravenous 0.005 mg/kg S(+) ketamine over 60 min at 3 (n=24; cohort 1), 12 h (n=8; cohort 3), and 24 h (n=8; cohort 2) after a single oral dose of 500 mg JNJ-40411813 or placebo. The pharmacokinetics and effects of JNJ-40411813 on cognition and subjective awareness were evaluated. Plasma JNJ-40411813 exposure was dose-dependent, t max ranged from 3-4 h and t 1/2 19.4-34.2 h across the dose levels. JNJ-40411813 significantly (p=0.02) reduced continuity of attention score (150 mg dose) and ameliorated smoking withdrawal-induced changes in power of attention and quality of episodic memory versus placebo. A modest reduction in alertness was observed at 150-225 mg doses, JNJ-40411813 (500 mg) reduced S(+) ketamine-induced negative symptom...Continue Reading

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References

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Citations

Jan 26, 2016·Progress in Neuro-psychopharmacology & Biological Psychiatry·Justine M KentMarc Ceusters
Feb 19, 2015·Pharmacology Research & Perspectives·Hilde LavreysenAnton Megens
Sep 12, 2015·Biological Psychiatry·Kari A Johnson, David M Lovinger
Jun 1, 2016·Frontiers in Pharmacology·Carolina MuguruzaLuis F Callado
Sep 23, 2016·Genes, Brain, and Behavior·M HeiligW H Sommer
Oct 30, 2019·Current Topics in Medicinal Chemistry·Junliang Hao, Qi Chen
Nov 29, 2016·Frontiers in Cellular Neuroscience·Kari A Johnson, David M Lovinger
Apr 28, 2017·Molecular Brain·James MaksymetzP Jeffrey Conn
Dec 29, 2020·Pharmacology & Therapeutics·Ewa Niedzielska-AndresEdmund Przegaliński
Mar 16, 2021·Expert Opinion on Therapeutic Patents·Alshaima'a M Qunies, Kyle A Emmitte
May 1, 2021·Journal of Clinical Medicine·Waldemar Kryszkowski, Tomasz Boczek
Mar 19, 2020·ACS Medicinal Chemistry Letters·Ana Isabel de LucasJosé María Cid

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