Pentobarbital: Dangerous, deadly and controversial

Clinical
By
Dr Leigh Dayton
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Pentobarbital

Regulatory bodies restrict it, but pentobarbital is still useful.

Pentobarbital has a bad reputation. Better known by its famous brand name, Nembutal, the barbiturate was linked to the 1962 death of film star Marilyn Monroe.1 Plus, in the early 2000s pentobarbital became the drug of choice for lethal injections of convicted criminals in the United States.2

It also has a long history. Pentobarbital was first prepared in 1864 by a young German chemist, J. F. W. Adolph von Baeyer, who for his effort won the 1905 Nobel Prize for Chemistry.3

It was manufactured as a sedative or anaesthetic in the 1920s when the Mayo Clinic’s John Lundy took interest in early experimental and clinical studies with barbiturates. Lundy began using them clinically, and in the 1930s is credited with naming Nembutal from the sodium salt structure of the drug: Na (sodium) ethyl + methyl + butyl + al.3

Throughout the 1940s and 1950s clinicians prescribed short-acting pentobarbitals as a sedative and hypnotic.

The downfall

Then Marilyn Monroe died. When it was ruled a suicide, her death gave pentobarbital a negative public profile, not helped by widespread abuse of Nembutal, its distinctive yellow capsules known on the streets as “yellow jackets”.4

And when pentobarbital began replacing drugs traditionally used for capital punishment, its reputation nosedived. Anti-pentobarbital pressure became so intense that in 2011 the Chief Executive of Nembutal manufacturer Lundbeck Pharmaceuticals, announced the Danish company would restrict sales to states conducting lethal injections.5

The resulting shortage left the 32 death-penalty states scrambling to find new drug protocols.6 In July last year US Attorney General William Barr directed the Federal Bureau of Prisons to use only pentobarbital in executions.7

Previously, prisons used a three-drug combination of sodium thiopental, along with pancuronium bromide and potassium chloride.7

Some states have already used pentobarbital for executions including Texas, Missouri and Georgia.7

How it works

Pentobarbital is highly lethal in overdose, triggering respiratory and nervous system failure.8 It works by activating GABA A receptors, causing enhanced GABA binding and opening of transmembrane chloride channels. The result: cellular hyperpolarisation within the central nervous system.9

Use in Australia

While pentobarbital is used in animal research and veterinary care, it was removed from the PBS schedule in 1980, a federal Department of Health spokesman confirmed to AP. It can be accessed via the Special Access Scheme.

References

  1. De Entrambasaguas Insomnia and death of Marilyn Monroe. Sleep Medicine 2013;14(1):e116. At: www.sciencedirect.com/science/article/abs/pii/S1389945713014718
  2. Denno DW. Lethal injection. Encyclopædia Britannica 2012. At: britannica.com/topic/lethal-injection
  3. Dundee JW, McIlroy PDA. The History of the barbiturates. Anesthesia 1982;37:726–8. At: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2044.1982.tb01310.x
  4. Barbiturate Abuse. At: www.webmd.com/mental-health/addiction/barbiturate-abuse#1
  5. Open letter to Ulf Wiinberg, Chief Executive of Lundbeck Pharmaceuticals – Response from Lundbeck Ulf Wiinberg, Lancet 2011;377(9783):2079. At: https://www.ncbi.nlm.nih.gov/pubmed/21663952
  6. Levitt R, Feyerick D. Death penalty states scramble for lethal injection drugs. CNN, 16 November 2013. At: https://edition.cnn.com/2013/11/15/justice/states-lethal-injection-drugs/index.html
  7. United States Department of Justice. Federal government to resume capital punishment after nearly two decade lapse. 2019. At: justice.gov/opa/pr/federal-government-resume-capital-punishment-after-nearly-two-decade-lapse
  8. National Institutes of Health. Daily Med. Label: Nembutal Sodium – sodium injection. At: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c380ab0-4386-48b6-80ab-ca594b23bc74
  9. Lester PA, Moore RM, Shuster KA, et al. Anesthesia and analgesia. In: The laboratory rabbit, guinea pig, hamster, and other rodents. Academic Press 2012:33–56. At: https://doi.org/10.1016/C2009-0-30495-X
  10. Special access scheme. Canberra: Australian Government, Therapeutic Goods Administration. At: www.tga.gov.au/form/special-access-scheme