The Pharmacology and Toxicology of the ‘Holy Trinity’

@article{Horsfall2017ThePA,
  title={The Pharmacology and Toxicology of the ‘Holy Trinity’},
  author={Joseph T Horsfall and Jon E. Sprague},
  journal={Basic \& Clinical Pharmacology \& Toxicology},
  year={2017},
  volume={120},
  pages={115–119}
}
Combining opioids with benzodiazepines and skeletal muscle relaxants ('The Holy Trinity') has been reported to potentiate the 'high'. Through unique interactions with colocalized μ-opioid and GABAA receptors, the combined use of these agents induces a synergistic increase in dopamine in the nucleus accumbens (NAc) and depression of respiration. The inhibition of GABA release mediated by μ1 -opioid receptor activation results in a subsequent increase in dopamine in the NAc. Benzodiazepines… 

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References

SHOWING 1-10 OF 37 REFERENCES

Mechanisms of fatal opioid overdose.

Better understanding of the role of heroin metabolites, the metabolism of methadone, drug interactions and tolerance would all be of considerable value in knowing how best to respond to this problem.

Mechanisms of fatal opioid overdose. - PubMed - NCBI

  • Biology, Medicine
  • 2016
Better understanding of the role of heroin metabolites, the metabolism of methadone, drug interactions and tolerance would all be of considerable value in knowing how best to respond to this problem.

Carisoprodol-Mediated Modulation of GABAA Receptors: In Vitro and in Vivo Studies

The results of these studies in vivo and in vitro collectively suggest the barbiturate-like effects of carisoprodol may not be due solely to its metabolite, meprobamate, and probably contribute to the abuse potential of this drug.

Flumazenil reversal of carisoprodol (Soma) intoxication.

Differential regulation of γ‐aminobutyric acid receptor channels by diazepam and phenobarbital

The results suggest that diazepam binds to a site that may enhance single channel burst frequency by increasing the affinity of GABA binding, while phenobarbital may stabilize the bursting open state of the channel by binding to a different modulatory site at or near the chloride channel.

Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital.

The results suggest that diazepam binds to a site that may enhance single channel burst frequency by increasing the affinity of GABA binding, while phenobarbital may stabilize the bursting open state of the channel by binding to a different modulatory site at or near the chloride channel.

Ventilatory effects of single, high‐dose triazolam in awake human subjects

It is concluded that a single dose of triazolam at two and three times the usual level does not cause respiratory depression in awake, normal subjects but does alter respiratory cycle timing causing an increase in breathing frequency.