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Fentanyls are solid analgesic–anaesthetics used in human and veterinary medicine. The science relevant to their use in defence and security is presented in this chapter. This includes a timeline of the pharmaceutical development of fentanyls and their medicinal uses. Their rise to prominence as incapacitating agents occurred when the Russian Special Forces used a mixture of two fentanyls, carfentanil and remifentanil, to facilitate resolution of the Moscow Theatre Siege in 2002. The identification of the composition of the mixture, enabled by analysis of clothing and a urine sample from the casualties, is described. A resurgence of apparent military interest in fentanyls by some Governments underpins the importance of developing a better awareness of the dangers posed by these toxic chemicals. This chapter discusses how research about the biological effects and chemistry of fentanyls serves as an information source to support the Chemical Weapons Convention (CWC).

On October 26, 2002, Russian Special Forces deployed a chemical aerosol against Chechen terrorists to rescue hostages in the Dubrovka theatre. Its use confirmed Russian military interest in chemicals with effects on personnel and caused 125 deaths through a combination of the aerosol and inadequate medical care. This study provides evidence from liquid chromatography-tandem mass spectrometry analysis of extracts of clothing from two British survivors, and urine from a third survivor, that the aerosol comprised a mixture of two anaesthetics--carfentanil and remifentanil--whose relative proportions this study was unable to identify. Carfentanil and remifentanil were found on a shirt sample and a metabolite called norcarfentanil was found in a urine sample. This metabolite probably originated from carfentanil.

Two children presented with an isolated foot and ankle deformity. Examination in each suggested a plexiform neurofibroma although this diagnosis had not been considered before referral. Diagnosis of neurofibromatosis type 1 was confirmed by MRI scanning and on investigation both patients were proved to have widespread disease. One had a plexiform neurofibroma encasing the aorta and oesophagus. Both cases remain under observation and have not undergone surgery for their disease. Neurofibromatosis can present with isolated foot and ankle deformity and when such a diagnosis is suspected thorough investigation is important in a condition in which unsuspected widespread disease may exist.

We show that the physiological activity of solid aerosolized benzylidenemalononitriles (BMNs) including ‘tear gas’ (CS) in historic human volunteer trials correlates with activation of the human transient receptor potential ankyrin 1 ion channel (hTRPA1). This suggests that the irritation caused by the most potent of these compounds results from activation of this channel. We prepared 50 BMNs and measured their hTRPA1 agonist potencies. A mechanism of action consistent with their physiological activity, involving their dissolution in water on contaminated body surfaces, cell membrane penetration and reversible thiolation by a cysteine residue of hTRPA1, supported by data from nuclear magnetic resonance experiments with a model thiol, explains the structure–activity relationships. The correlation provides evidence that hTRPA1 is a receptor for irritants on nociceptive neurons involved in pain perception; thus, its activation in the eye, nose, mouth and skin would explain the symptoms of lachrymation, sneezing, coughing and stinging, respectively. The structure–activity results and the use of the BMNs as pharmacological tools in future by other researchers may contribute to a better understanding of the TRPA1 channel in humans (and other animals) and help facilitate the discovery of treatments for human diseases involving this receptor.