A Brief History of Pentobarbital

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For those curious about the discovery of barbiturates, their origin can be traced back to Germany in 1864.  Ludwig von Baeyer, the founding father of the Bayer company, synthesized urea (a natural bi-product of the body) with malonic acid (derived from applies) to create barbituric acid.  The term ‘barbituric’ is said to have arisen from either the Saint Barbara, being celebrated in the region at the time of the discovery, or to show his affection for a girl named Barbara. Studies revealed that barbituric acid was poorly absorbed from the gut and lacked any real impact in the body. It was later transformed by Josef von Mering and Emil Fisher into the barbiturate compound we know today.  Given the earlier name Veronal, it was a drug used for insomnia and other anxiety disorders. Eventually it found its way into veterinary medicine as an anesthetic drug that when overdosed, led to a swift and peaceful death. The term barbital was patented by Fisher in 1903.

Barbiturates rapidly became the leading non-inhalant drug used in animal euthanasia, as mentioned in the 1963 version of the AVMA Euthanasia Guidelines.  Deemed the gentlest of the ‘poisons’, barbiturate overdoses lead to rapid unconsciousness, cessation of breathing, and cardiac arrest. Unconsciousness first was a guarantee before cardiac arrest so veterinarians could be certain awareness of death was nonexistent for the dying animal. This class of drug met all of the 14 criteria of method selection, save for a few, and even then, proper storage of barbiturates and disposal of the body was all it took to keep them top of the pack.  Pure barbiturates held human abuse potential, and in 1972, were raised up from a Category III to a Category II controlled drug in the US. In an effort to reduce this abuse potential, synergistic drugs were added in to pure pentobarbital to increase safety and reduce some brands back down to Category IIIs. The best example of this is phenytoin sodium, a cardio-toxic substance.  

Pentobarbital was originally only available in powder form.  Veterinary services had to mix it precisely with the right type of water, alcohol, or other diluents and often found it unstable or with the wrong pH.  In the early 1980’s, North American Pharmacal, now Vortech Pharmaceuticals, found the right packaging and preservative formula that allowed room temp water to be added to the powder for easy storage and administration.  Eventually, pentobarbital could be purchased in liquid form making handling even easier. Other forms of barbiturates exist today that are considered short acting, long acting, better for some symptoms compared to others, and so on.  In brief, pentobarbital remains the most advanced drug for animal euthanasia, and will until something better comes along.  

References

Jones, AW. Perspectives in Drug Discovery. Ln: Essays on the history and development of pharmaceutical substances. Sweden. Dept of Forensic Genetics and Toxicology; 2010. p. 20  

AVMA 2013 Guidelines for the Euthanasia of Animals https://www.avma.org/KB/Policies/Documents/euthanasia.pdf
Accessed September 18, 2019.

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Kathleen Cooney

DVM, CHPV, CCFPFounder, Director of Education for the Companion Animal Euthanasia Training Academy
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