Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Dhwanil A DalwadiJohn A Schetz


Efavirenz is highly effective at suppressing HIV-1, and the WHO guidelines list it as a component of the first-line antiretroviral (ARV) therapies for treatment-naïve patients. Though the pharmacological basis is unclear, efavirenz is commonly associated with a risk for neuropsychiatric adverse events (NPAEs) when taken at the prescribed dose. In many patients these NPAEs appear to subside after several weeks of treatment, though long-term studies show that in some patients the NPAEs persist. In a recent study focusing on the abuse potential of efavirenz, its receptor psychopharmacology was reported to include interactions with a number of established molecular targets for known drugs of abuse, and it displayed a prevailing behavioral profile in rodents resembling an LSD-like activity. In this report, we discovered interactions with additional serotonergic targets that may be associated with efavirenz-induced NPAEs. The most robust interactions were with 5-HT3A and 5-HT6 receptors, with more modest interactions noted for the 5-HT2B receptor and monoamine oxidase A. From a molecular mechanistic perspective, efavirenz acts as a 5-HT6 receptor inverse agonist of Gs-signaling, 5-HT2A and 5-HT2C antagonist of Gq-signaling, and a blo...Continue Reading


Mar 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·J F TallmanR C Henneberry
Sep 15, 1992·Annals of Internal Medicine·G X McLeod, S M Hammer
Jun 17, 1988·JAMA : the Journal of the American Medical Association·S MaxwellK Busch
Dec 1, 1984·Paraplegia·J H Baker, J R Silver
Nov 1, 1980·Anaesthesia·G J Arthurs, R Davies
May 1, 1997·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·F X VollenweiderJ Angst
May 26, 1998·Psychopharmacology·C T EganM Teitler
Nov 26, 1999·Cellular Signalling·N AncellinA Morel
Oct 18, 2000·Journal of Pharmacological and Toxicological Methods·S L ArmourW J Chen
Aug 18, 2001·Pharmacology, Biochemistry, and Behavior·S P VickersG A Kennett
Nov 15, 2001·Journal of Acquired Immune Deficiency Syndromes : JAIDS·M NúñezV Soriano
Apr 16, 2002·BMJ : British Medical Journal·M E Jan WiseS Reid
Feb 1, 1963·British Journal of Pharmacology and Chemotherapy·S J CORNEB T WARNER
Apr 9, 2005·The Journal of Pharmacology and Experimental Therapeutics·Paromita Das, Glenn H Dillon
Nov 4, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Félix GutiérrezAlberto Martín-Hidalgo
Nov 17, 2005·Annals of Internal Medicine·David B CliffordRoy M Gulick
Jun 17, 2006·Pharmaceutical Research·Grégoire DirsonRobert Farinotti
May 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jean-Claude BéïqueRodrigo Andrade
Apr 5, 2008·Molecular Pharmacology·Jiansong LuoJeffrey L Benovic
Jul 18, 2008·Anesthesia and Analgesia·Camilo RojasBarbara Slusher
Oct 7, 2008·Archives of Gerontology and Geriatrics·Sang Won SeoDuk L Na
Dec 6, 2008·Obesity·Steven R SmithUNKNOWN APD356-004 Study Group
Jul 8, 2009·Annals of Internal Medicine·Alicia Gutiérrez-ValenciaUNKNOWN Sociedad Andaluza de Enfermedades Infecciosas
Oct 14, 2009·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Odd Martin VallersnesInge-André Rasmussen
Dec 17, 2009·Neurotoxicity Research·Pedro R T RomãoElaine C Gavioli

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