Possible antidote for club drug GHB overdose

Date:
August 23, 2021
Source:
University at Buffalo
Summary:
Diclofenac and other NSAIDs may limit the passage of narcolepsy
medication and illicit party drug GHB to the brain, decreasing
the potential for fatal overdose, researchers find.



FULL STORY ========================================================================== Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) may
limit the passage of gamma hydroxybutyric acid (a narcolepsy medication
and illicit party drug commonly known as GHB) to the brain, decreasing the potential for fatal overdose, according to a University at Buffalo study.


==========================================================================
The research found that treatment with diclofenac after taking GHB
led to decreased concentrations of GHB in the brain and an improved respiration. The study, completed in animal models, was published in Biopharmaceutics & Drug Disposition. Previous studies completed by the UB researchers found that the NSAIDs ibuprofen and ketoprofen also affected
the movement of GHB in the body.

GHB is approved for a number of clinical uses, including the treatment
of narcolepsy, a chronic sleep disorder, and alcoholism. However,
GHB prescriptions are limited due to its high potential for abuse as
a club and date-rape drug. At high doses, the drug can cause amnesia, drowsiness and depressed breathing. There are currently no approved
antidotes for GHB overdose.

"The therapeutic utility of GHB in the treatment of narcolepsy [as Xyrem]
has been overshadowed by its high prevalence of abuse. The abuse of GHB
-- known as Fantasy, Liquid Ecstasy and G -- carries the risk of severe
adverse effects including sedation, respiratory depression, hypothermia,
coma and death," says Marilyn Morris, PhD, SUNY Distinguished Professor
and chair of the Department of Pharmaceutical Sciences in the UB School
of Pharmacy and Pharmaceutical Sciences.

"Current treatment of GHB overdose is limited to supportive care. My
laboratory has identified MCT1 inhibitors as a treatment strategy to
prevent death after GHB overdoses. In this research, we identified the
NSAID diclofenac as a MCT1 inhibitor and demonstrated its effectiveness as
a potential antidote for GHB overdose. Also, our findings significantly
suggest that diclofenac and other NSAIDs may decrease the effectiveness
of Xyrem used in the treatment of narcolepsy." Additional investigators include first author, UB alumna and former graduate student in Morris'
lab Vivian Rodriguez-Cruz, PhD, research scientist at Eli Lilly and
Company; and Tianjing Ren, PhD, postdoctoral researcher in the UB School
of Pharmacy and Pharmaceutical Sciences.

Commonly sold under the brand name Voltaren, diclofenac is prescribed to
treat pain and inflammation. Morris' lab has found that some NSAIDs can
block tissue uptake of drugs by monocarboxylate transporters (MCTs), a
family of proteins that transport molecules across biological membranes, including the blood-brain barrier, which protects the brain from toxins
and pathogens circulating in the blood while allowing for the passage
of nutrients.

GHB relies on MCTs for transport throughout the body, making the study
of the inhibition of MCTs as an antidote a focus of Morris' lab.

The recent study sought to understand the impact diclofenac has on GHB
toxicity by measuring the effect of their interaction on respiratory
depression -- the main cause of death following GHB overdose.

Diclofenac was found to inhibit the brain uptake of GHB by MCT1, the
only monocarboxylate transporter present at the blood-brain barrier,
resulting in a reversal of respiratory depression after GHB overdose.

========================================================================== Story Source: Materials provided by University_at_Buffalo. Original
written by Marcene Robinson. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Vivian Rodriguez‐Cruz, Tianjing Ren, Marilyn E. Morris.

Drug‐drug interaction between diclofenac and
gamma‐hydroxybutyric acid. Biopharmaceutics & Drug
Disposition, 2021; DOI: 10.1002/bdd.2296 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210823125711.htm

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