γ-Hydroxybutyrate (GHB)-induced respiratory depression: combined receptor-transporter inhibition therapy for treatment in GHB overdose.

Molecular Pharmacology
Bridget L MorseMarilyn E Morris

Abstract

Overdose of γ-hydroxybutyrate (GHB) frequently causes respiratory depression, occasionally resulting in death; however, little is known about the dose-response relationship or effects of potential overdose treatment strategies on GHB-induced respiratory depression. In these studies, the parameters of respiratory rate, tidal volume, and minute volume were measured using whole-body plethysmography in rats administered GHB. Intravenous doses of 200, 600, and 1500 mg/kg were administered to assess the dose-dependent effects of GHB on respiration. To determine the receptors involved in GHB-induced respiratory depression, a specific GABA(B) receptor antagonist, (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911), and a specific GABA(A) receptor antagonist, bicuculline, were administered before GHB. The potential therapeutic strategies of receptor inhibition and monocarboxylate transporter (MCT) inhibition were assessed by inhibitor administration 5 min after GHB. The primary effect of GHB on respiration was a dose-dependent decrease in respiratory rate, accompanied by an increase in tidal volume, resulting in little change in minute volume. Pretreatment with 150 mg/kg SCH50911 completely prevented the decrease in respiratory rat...Continue Reading

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Citations

May 3, 2013·Clinical Reviews in Allergy & Immunology·M E SutterT E Albertson
Feb 9, 2013·The Journal of Pharmacology and Experimental Therapeutics·Bridget L Morse, Marilyn E Morris
Jan 18, 2016·Forensic Science International : Synergy·Lena-Maria MehlingCornelius Hess
Jul 24, 2014·Journal of Psychoactive Drugs·Rebekah Brennan, Marie Claire Van Hout
Dec 11, 2014·Journal of Addiction Medicine·Rama M KamalCornelis A J De Jong
Jul 1, 2017·The American Journal of Drug and Alcohol Abuse·Bridget L MorseMarilyn E Morris
Dec 28, 2017·The AAPS Journal·Melanie A FelmleeMarilyn E Morris
Apr 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·Kristin E Follman, Marilyn E Morris
Jul 3, 2013·The Journal of Pharmacology and Experimental Therapeutics·Bridget L Morse, Marilyn E Morris
May 21, 2016·Journal of Clinical Pharmacology·C Michael White
Apr 7, 2020·Archives of Toxicology·Dino Luethi, Matthias E Liechti
Jan 9, 2021·The AAPS Journal·Melanie A FelmleeMarilyn E Morris
May 9, 2021·The Journal of Pharmacology and Experimental Therapeutics·Vivian Rodriguez-Cruz, Marilyn E Morris
Jul 1, 2021·Biopharmaceutics & Drug Disposition·Vivian Rodriguez-CruzMarilyn E Morris

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