Behavioral efficacy of diazepam against nerve agent exposure in rhesus monkeys

Castro, Carl A.; Larsen, Tom; Finger, A.V.; Solana, Richard P.; McMaster, S.B.

doi:10.1016/0091-3057(92)90076-r

Cited by 45 publications

(8 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although t max is also prolonged in animal primates, multiple animal studies, including replicate animal primate studies, consistently indicate that anticonvulsant, neuroprotective, cognitionprotecting, and lifesaving effects are conferred by IM diazepam when administered after exposure to otherwise lethal doses of nerve agents. [14][15][16][17][18][19][20] In most of these animal studies, IM diazepam was given in conjunction with pyridostigmine pretreatment plus atropine and pralidoxime treatment to emulate current US military doctrine for buddy-aid treatment of severe nerve agent poisoning when medical care is not immediately available.…”

Section: Discussionmentioning

confidence: 99%

Bioavailability and Dose Proportionality of Intramuscular Diazepam Administered by Autoinjector

Lehmann¹,

Wannarka

2008

The Journal of Clinical Pharma

View full text Add to dashboard Cite

A diazepam 10-mg autoinjector was evaluated in bioequivalence and dose proportionality studies; both involved 24 young, healthy subjects and used randomized, open-label, 2-treatment, 2-period crossover designs with a 3-week washout period between treatments. The bioequivalence study compared a single diazepam 10-mg autoinjector with a conventional needle and syringe containing 10 mg of diazepam injectable. The dose proportionality study compared the pharmacokinetics of a single diazepam 10-mg autoinjector with that of 2 diazepam 10-mg autoinjectors given simultaneously (20 mg). Injections were intramuscular in the midanterolateral thigh in both studies. The studies showed that the diazepam autoinjector produced consistent plasma diazepam levels, with a rapid onset of absorption. The diazepam 10-mg autoinjector given intramuscularly was bioequivalent to a conventional syringe containing diazepam 10 mg. A single (10-mg) autoinjector and 2 (20-mg) diazepam autoinjectors administered simultaneously produced plasma diazepam concentrations that were essentially dose proportional.

show abstract

Section: Discussionmentioning

confidence: 99%

Bioavailability and Dose Proportionality of Intramuscular Diazepam Administered by Autoinjector

Lehmann¹,

Wannarka

2008

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…To evaluate the behavioral impact of the exposures, performance on a serial probe recognition test (SPR) was used. The SPR is a visual list memory task that has been used previously to evaluate the effects of CWNA exposure in primates [4, 12]. Finally, blood was sampled before and after exposure to evaluate the soman‐induced inhibition of circulating cholinesterase activity.…”

Section: Introductionmentioning

confidence: 99%

ORIGINAL ARTICLE: Evaluation of miosis, behavior and cholinesterase inhibition from low‐level, whole‐body vapor exposure to soman in African green monkeys (Chlorocebus sabeus)*

Genovese

Benton²,

Oubre

et al. 2010

J of Medical Primatology

View full text Add to dashboard Cite

show abstract

“…Considering the delayed behavioural influences, it seems reasonable that by virtue of established neuroprotective efficacy diazepam should protect from incapacitation. Castro et al (1992) reported that the addition of diazepam to the therapy eliminated soman‐induced behavioural deficits in monkeys 6 days after challenge. In the case of combined atropine/diazepam therapy in rats, Philippens et al (1992) found that the combination of otherwise pharmacologically effective doses of atropine (2 mg/kg) and diazepam (0.625 mg/kg) did not protect from large decrements in performance of an earlier acquired active avoidance task 6 days after intoxication with a LD 50 of soman.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, potential behavioural interactions of atropine and diazepam, on their own and in the presence of dichlorvos, were sought to be determined. Finally, taking into account the long‐term neuroprotective role of the anticonvulsant diazepam, and hence, its delayed protective influences on behaviour (when combined with atropine at certain doses) (Castro et al 1992; Philippens et al 1992), this study also aimed at elucidating possible predictive value of acute behavioural testing.…”

mentioning

confidence: 99%

The Influence of Diazepam on Atropine Reversal of Behavioural Impairment in Dichlorvos‐Treated Rats

Savić

Obradović

Ugresic

et al. 2003

Pharmacology & Toxicology

View full text Add to dashboard Cite

Acute effects on the behaviour of the organophosphate insecticide dichlorvos and its standard antidotes possessing behavioural activity, atropine and diazepam, were studied separately and in combinations in male Wistar rats. In the spontaneous locomotor activity test, dichlorvos and diazepam decreased, whereas atropine increased performance. The effect of dichlorvos was obtained at a dose (5 mg/kg) that induced overt intoxication, and could not be reversed during first half hour-period after administration of any combination of drugs. In the other two tests, active avoidance learning and rotarod performance, the effective dose of dichlorvos (2 mg/kg) was devoid of somatic signs of intoxication. In these more sensitive tests, the effective atropine dose (40 mg/kg) completely reversed dichlorvos-induced incapacitation. In the rotarod test, diazepam (0.5 mg/kg) contributed to the incapacitating effect of dichlorvos, and impeded desirable influence of atropine as well. In the active avoidance test, diazepam (2.5 mg/kg) contributed to failure to escape; it did not influence the dichlorvos-induced decrease of avoidance performance, nor did it impair the completely reversing effects of atropine. The results point to the possible summation of acute incapacitating effects of organophosphates and diazepam on motor performance, which seems to be, at least partly, antagonized by sufficiently high doses of atropine. However, taking into account the long-term neuroprotective role of the anticonvulsant diazepam, and hence its delayed beneficial influences on behaviour, the immediate testing of atropine/diazepam treatment of organophosphate intoxication in active avoidance paradigm could possess beside sensitivity the predictive value as well.

show abstract

Behavioral efficacy of diazepam against nerve agent exposure in rhesus monkeys

Cited by 45 publications

References 13 publications

Bioavailability and Dose Proportionality of Intramuscular Diazepam Administered by Autoinjector

Bioavailability and Dose Proportionality of Intramuscular Diazepam Administered by Autoinjector

ORIGINAL ARTICLE: Evaluation of miosis, behavior and cholinesterase inhibition from low‐level, whole‐body vapor exposure to soman in African green monkeys (Chlorocebus sabeus)*

The Influence of Diazepam on Atropine Reversal of Behavioural Impairment in Dichlorvos‐Treated Rats

Contact Info

Product

Resources

About