Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus)

Muggleton, Neil G.; Bowditch, A.P.; Crofts, H. S.; Scott, Elizabeth; Pearce, P.C.

doi:10.1007/s00213-002-1324-7

Cited by 25 publications

(11 citation statements)

References 30 publications

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“…Typical symptoms that have been reported include tension, anxiety, difficulty in concentrating, slowness of recall, mental confusion and sleep disturbances (e.g., Sherman, 1995). Changes in cognitive function in marmosets following cholinergic disruption have also been reported e.g., Roberts et al, 1992, Muggleton et al, 2003 The electrocorticogram was recorded both during behavioural testing and during sleep using fully implantable radiotelemetry devices. This approach meant that there were no external connections or exit wounds and that restraint was not required to make recordings.…”

Section: Discussionmentioning

confidence: 97%

“…This included discrimination learning and memory elements, as well as rule reversals and attentional set shifting stages. The rationale for selection of these stages was that some of these have previously been shown to be affected by cholinergic lesions (e.g., Roberts et al, 1990) as well as AChE inhibitors (Muggleton et al, 2003). These stages, which might reasonably be expected to show shortterm effects following diazinon exposure, were supplemented by elements which might show alterations on the basis of the varied behavioural effects reported in the epidemiological literature, such as attention and memory (Rosenstock et al, 1991), as well as 'flexibility of thinking' and 'abstraction' (Savage et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

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A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

Muggleton¹,

Smith

Scott

et al. 2005

J Psychopharmacol

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The long-term sequelae of exposure to low doses of organophosphate compounds are ill defined, with effects variously reported on a range of indices of central nervous system functions such as sleep, cognitive performance and electroencephalogram (EEG). These indices were examined in common marmosets exposed to a range of doses of the organophosphorous sheep dip, diazinon. Cognitive performance was assessed by means of elements from the Cambridge Neuropsychological Test Automated Battery (CANTAB), and radiotelemetry techniques were employed to monitor the electrocorticogram and sleep patterns. Data were collected for 12 months following intramuscular administration of a single dose of diazinon (10, 90 or 130 mg.kg (-1)) or vehicle. Although high levels of erythrocyte acetylcholinesterase (AChE) inhibition (up to 82%) and short-term changes in sleep patterns were seen, there was no evidence of biologically significant long-term changes in any measures. The effects of multiple exposures, impurities or mixtures of OP compounds remain to be investigated.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

Muggleton¹,

Smith

Scott

et al. 2005

J Psychopharmacol

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“…Its efficacy has been suggested by animal studies using dogs [17] and marmoset monkeys [18]. Furthermore, butyrylcholinesterase, a scavenger enzyme, appears promising.…”

Section: Othersmentioning

confidence: 97%

Effective Use of Drugs to Counter Chemical Terrorism

Okumura¹,

Hitomi²,

Hirahara

et al. 2009

CDTH

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In the present international climate, preparedness and effectively responding to chemical terrorism is of serious concern. Given that antidotes are available for chemical agents, such as nerve or blood (cyanide) agents, the key to survival is how quickly and effectively antidotes can be administered in mass casualty events. To counter agents acting on the nervous system, atropine, pralidoxime and diazepam are generally administered, but aside from pralidoxime, no general consensus has been reached regarding the use of oximes, such as obidoxime and HI-6. In addition, the use of diazepam is being investigated in comparison to other benzodiazepines. As antidotes to blood agents, sodium nitrite (or amyl nitrite) and sodium thiosulfate are often used in the United States, but in Europe, dicobalt edetate and hydroxocobalamin are used. In particular, hydroxocobalamin appears to be a promising antidote against blood-agent terrorism. In mass casualty events caused by chemical terrorism, it is also necessary to consider the most effective administration routes of the antidote (intravenous, intramuscular or intraosseous). Hence, it is imperative to adequately discuss when first responders (rescuers) wearing personal protective equipment (PPE) should administer these drugs and who should be in charge of such drug administration. Here these problems are reviewed and discussed with reference to the current literature.

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“…For these reasons, there is a need to find an alternative monkey species to evaluate nerve agent toxicity and medical countermeasures against chemical warfare nerve agents. Two other NHP species, the cynomolgus monkey (Macaca fascicularis) (Carpentier et al 2001;Krummer et al 2002;Lenz et al 2005;Lallement et al 1997Lallement et al , 1998Lallement et al , 1999Lallement et al , 2000Lallement et al , 2002von Bredow et al 1991) and the common marmoset (Callithrix jacchus) (D'Mello and Scott 1986;Muggleton et al 2003;Wetherell and French 1991;van der Schans et al 2003;van Helden et al 1992van Helden et al , 2003van Helden et al , 2004avan Helden et al , 2004bBusker et al 1996;Philippens et al 2000), have been used in this regard. Both of these species have drawbacks.…”

Section: Introductionmentioning

confidence: 97%

The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

Despain

McDonough

McMonagle

et al. 2007

Toxicology Mechanisms and Methods

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This study determines soman toxicity in African green monkeys (Chlorocebus aethiops) and is the first step in exploring the suitability of this species as a model for nerve agent studies. Male African green monkeys were surgically implanted with telemetry devices to monitor electroencephalographic (EEG) and electrocardiographic (ECG) activity. Blood was taken at various times to measure whole blood acetylcholinesterase (AChE) activity and cardiac troponin I (cTnI). Blood AChE activity relative to baseline was 0.0% to 2.5% 6 h after soman exposure and recovered to 31.9% to 72.0% by 30 days after exposure. The 6 h postexposure cTnI levels varied from 0.64 to 6.55 ng/mL, suggesting cardiac damage. Soman was prepared in saline to a concentration of 100 mug/mL. Using an up-down design for small samples, subjects were exposed to 5.01, 6.31, or 7.94 mug/kg soman IM. The first subject was given 5.01 mug/kg soman IM and survived. Three subjects received 6.31 mug/kg soman IM and survived. Three subjects received 7.94 mug/kg soman IM and died within 25 min, 26 min, or 6 h. In all subjects, toxic signs of muscle fasciculation, tremors, chewing, and profuse salivation developed within 2 to 7 min. Tonic-clonic motor convulsions and EEG seizure began between 2 and 18 min after tremor onset. The 48 h IM LD50 of soman in saline in the African green monkey was calculated to be 7.15 mug/kg. The signs and speed of soman intoxication in African green monkeys were consistent with those described in rhesus, cynomolguscynomolgus, and baboons.

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Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus)

Cited by 25 publications

References 30 publications

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

Effective Use of Drugs to Counter Chemical Terrorism

The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

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