Evaluation of two scopolamine and physostigmine pretreatment regimens against nerve agent poisoning in the dog

Abstract

Currently, there is no viable protection against chemical warfare agents for the working dog. Physostigmine (PHY) and scopolamine (SCO) have been shown to protect dogs against nerve agents with minimal side effects. The goal of this study was to investigate whether reported protective SCO/PHY plasma concentrations of 0.2 and 0.7 ng/mL, respectively, could be reached and maintained with minimal side-effects thereby identifying possible pretreatment regimens. Two continuous regimens of SCO/PHY were administered to beagle dogs. The first regimen consisted of administering transdermal SCO and intraocular PHY, the second consisted of transdermal SCO and rectal PHY. SCO/PHY plasma concentrations for each regimen were determined, individual protective times were calculated and a computerized pharmacokinetic analysis was performed. The results showed transdermal SCO and intraocular PHY routes of delivery achieved sustained protective drug concentrations with minimal side-effects and the rectal route of delivery did not. Group median protective times for the first regimen were 54.45 h for SCO and 64.35 h for PHY, and for the second regimen 63.75 h for SCO and 0 h for PHY. The combined transdermal patch and intraocular regimen may provide a safe and effective regimen against nerve agent poisoning in dogs.

Sniffing with mass spectrometry

“…Currently available devices, however, suffer from ineffectual quantification in the simultaneous analysis of mixtures of multiple gaseous compounds [4]. The olfaction of sniffer animals (e.g., patrol dogs), on the other hand, is sensitive to various odor molecules and is invaluable for judicial expertise, but animals are vulnerable to poisoning with toxic substances such as viruses and chemical warfare agents (e.g., nerve agents) [5,6]. Therefore, an alternative approach with multiple detection channels and tolerance to poison is highly desired for efficient detection of multiple gaseous/volatile molecules in ambient conditions [4,7,8].…”

Reversal of cardiac vagal effects of physostigmine by adjunctive muscarinic blockade

“…(Bonhage et al, 2009;Lim et al, 1991;Lim et al, 1988;Muggleton et al, 2003;Philippens et al, 1998;Philippens et al, 2000;von Bredow et al, 1991;Wetherell et al, 2002;Wetherell, 1994) Pyridostigmine (a quaternary compound restricted primarily to the peripheral nervous system) and physostigmine (a neutral compound which can more readily pass the blood brain barrier) are long acting, but reversible, AChE inhibitors that are effective pre-treatments for nerve-agent exposure. While both agents are effective in preventing lethality in animal studies, physostigmine appears to be more effective against incapacitation, most likely as a consequence of its combined central and peripheral actions.…”