The history of barbiturates a century after their clinical introduction

Abstract

The present work offers an analysis of the historical development of the discovery and use of barbiturates in the field of psychiatry and neurology, a century after their clinical introduction. Beginning with the synthesis of malonylurea by von Baeyer in 1864, and up to the decline of barbiturate therapy in the 1960s, it describes the discovery of the sedative properties of barbital, by von Mering and Fischer (1903), the subsequent synthesis of phenobarbital by this same group (1911), and the gradual clinical incorporation of different barbiturates (butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, etc). We describe the role played in therapy by barbiturates throughout their history: their traditional use as sedative and hypnotic agents, their use with schizophrenic patients in so-called "sleep cures" (Klaesi, Cloetta), the discovery of the antiepileptic properties of phenobarbital (Hauptmann) and their use in the treatment of epilepsy, and the introduction of thiobarbiturates in intravenous anesthesia (Lundy, Waters). We also analyze, from the historical perspective, the problems of safety (phenomena of dependence and death by overdose) which, accompanied by the introduction of a range of psychoactive drugs in the 1950s, brought an end to barbiturate use, except in specific applications, such as the induction of anesthesia and the treatment of certain types of epileptic crisis.

Keywords: anesthesia; barbiturates; epilepsy; history of medicine; sedative-hypnotic drugs; “sleep cures”.

Figure 1

Synthesis of barbituric acid, from the combination of malonic acid (left) and urea (right).

Figure 2

(a) Adolf von Baeyer (1835–1917); (b) Josef von Mering (1849–1908); (c) Emil Fischer (1852–1919).

Figure 3

(a) Elixir Veronal from Dr Bustamante’s Laboratories it is a “Practical treatment of insomnia”. They have also added audaciously “Secure and harmless”. Finally they say that “it tastes good and acts smoothly, being absorbed by the organism”. (b) Advertisement for Abbott sodium pentobarbital in an American medical journal of 1933, highlighting its “short but powerful hypnotic effect and prolonged sedative action from small dosage”.

Figure 4

The packaging of Somnifen^®, produced by Hoffmann-LaRoche.

Figure 5

The packaging of Abbott Pentothal^® at the time of its clinical introduction in the late 1930s. Pieces from the Museum of the Buenos Aires Anaesthesiology Association (Argentina).

Figure 6

Evolution of annual barbiturates production in USA for the period 1941–1960. Adapted from Fort (1964).

Figure 7

Death certificate of the actress Marilyn Monroe, issued on 28th August 1962. The circles indicate cause of death (“Acute barbiturate poisoning. Ingestion of overdose”) and the intentionality (“Probable suicide”)

Figure 8

Deaths from overdose of barbiturates in England and Wales during the period 1905–1960 (Registrar-General’s Statistical Review for England and Wales). Includes both accidental deaths and suicides. Adapted from Glatt (1962).