Effect of diphenhydramine on organophosphorus insecticide toxicity in mice

Mohammad, F. K.; Al-Kassim, N. A. H.; Abdul-Latif, A.R.

doi:10.1016/0300-483x(89)90107-8

Cited by 16 publications

(14 citation statements)

References 11 publications

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“…The selections of the doses of diphenhydramine in the present study were based on our preliminary experiments in chicks and on the literature (Mohammad et al, 1989;Mohammad and Basher, 1995;Faris and Mohammad, 1996a, b;Mohammad et al 2002). The Scientific Committee of the College of Veterinary Medicine at the University of Mosul has approved the present experiments in chicks.…”

Section: Methodsmentioning

confidence: 99%

“…Several recent studies evaluated the potential neurotoxicity and/or behavioral profiles of the drug in man or laboratory animals (Holger et al, 2002;Gupta et al, 2004;Khanwelkar et al, 2008;Van Ruitenbeek et al, 2010;Feltner and Haig, 2011). Diphenhydramine is also a potential alternative antidote against organophosphate and carba-mate insecticides poisoning, as it mainly reduces the muscarinic, nicotinic and CNS effects of cholinergic overstimulation (Mohammad et al, 1989;Faris and Mohammad, 1996a;Bird et al, 2002). The drug is clinically used in the avian species to counteract feather damaging behavioral cycle (Doneley and Doneley, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Acute Toxicity and Neurobehavioral Effects of Diphenhydramine in Chicks

2012

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The present study was undertaken to examine the acute toxicity (LD50) and neurobehavioral manifestations in the open-field activity and tonic immobility tests in 7-14 day-old chicks treated with the H1-receptor antagonist diphenhydramine. Plasma and whole brain cholinesterase activities were also determined in the chicks. The LD50 of diphenhydramine in chicks was 49.3 mg/kg, intramuscularly (i.m.). The signs of diphenhydramine toxicosis in the chicks which appeared within one hour after injection included excitation, jumping, whole body tremor, ataxia, gasping, frequent defecation, paralysis and recumbency. Fifteen minutes after i.m. injection, diphenhydramine at 2.5 and 5 mg/kg decreased the general locomotor activity of the chicks in the 5-min open-field activity test, as seen by a significant increase in the latency to move from the center of the open-field arena and decreases in the numbers of lines crossed and escape jumps in comparison with control values. Diphenhydramine significantly decreased the frequencies of pecking and defecation only at 5 mg/kg when compared with respective control values. Diphenhydramine treatments at 2.5 and 5 mg/kg also significantly increased the durations of tonic immobility of the chicks and decreased their whole brain cholinesterase activity by 33 and 30%, respectively, in comparison with the control values. In conclusion, the data suggest that diphenhydramine induces central nervous system depression in chicks at doses below the LD50 value of the drug which is reported here for the first time.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acute Toxicity and Neurobehavioral Effects of Diphenhydramine in Chicks

2012

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“…Though the current emergency medicine treatment for organophosphate insecticide (OP) poisoning in mammals is atropine, diphenhydramine (DPH), the active ingredient in Benadryl® and several other human medicines, is considered as an alternative treatment because DPH competitively inhibits the acetylcholine (ACh) receptor, and thus protects against OP poisoning caused by hyperstimulation from acetylcholinesterase inhibition (22)(23)(24). Thus, the overarching objective of this study was to test a read-across hypothesis for DPH protection against diazinon (DZN; a model OP) toxicity in the aquatic invertebrate, Daphnia magna, and the vertebrate, Danio rerio.…”

Section: Introductionmentioning

confidence: 99%

Comparative Pharmacology and Toxicology of Pharmaceuticals in the Environment: Diphenhydramine Protection of Diazinon Toxicity in Danio rerio but Not Daphnia magna

Kristofco

Chambliss

et al. 2014

AAPS J

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Abstract. Pharmaceuticals and other contaminants of emerging concern present unique challenges to environmental risk assessment and management. Fortunately, mammalian pharmacology and toxicology safety data are more readily available for pharmaceuticals than other environmental contaminants. Identifying approaches to read-across such pharmaceutical safety information to non-target species represents a major research need to assess environmental hazards. Here, we tested a biological readacross hypothesis from emergency medicine with common aquatic invertebrate and vertebrate models. In mammals, the antihistamine diphenhydramine (DPH) confers protection from poisoning by acetylcholinesterase inhibition because DPH blocks the acetylcholine receptor. We employed standardized toxicity methods to examine individual and mixture toxicity of DPH and the acetylcholinesterase inhibitor diazinon (DZN) in Daphnia magna (an invertebrate) and Danio rerio (zebrafish, a vertebrate). Though the standardized Fish Embryo Toxicity method evaluates early life stage toxicity of zebrafish (0-3 days post fertilization, dpf), we further evaluated DPH, DZN, and their equipotent mixture during three development stages (0-3, 3-6, 7-10 dpf) in zebrafish embryos. Independent action and concentration addition mixture models and fish plasma modeling were used to assist interpretation of mixture toxicity experiments. Though our primary hypothesis was not confirmed in acute studies with Daphnia magna, DPH conferred a protective effect for acute DZN toxicity to zebrafish when DPH plasma levels were expected to be greater than mammalian therapeutic, but lower than acutely lethal, internal doses. We further observed that timing of developmental exposure influenced the magnitude of DZN and DPH toxicity to zebrafish, which suggests that future zebrafish toxicity studies with pharmaceuticals and pesticides should examine exposure during developmental stages.KEY WORDS: alternative toxicity test methods; biological read-across; comparative pharmacology and toxicology; mixture toxicology; pharmaceuticals in the environment.

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“…It was chosen for use in this protocol because it produces a classic cholinergic toxidrome. 4,7 This dose of dichlorvos represents approximately two times the subcutaneous LD 50 and was chosen to present a severe exposure with high mortality, thereby decreasing the number of animals required to demonstrate statistically significant efficacy. Mortality (cessation of movement, including respiration), the primary outcome measure, was assessed by two investigators and recorded at 10 minutes and confirmed by continued observation for at least one hour.…”

Section: Study Protocolmentioning

confidence: 99%

“…Diphenhydramine chloride (DPH), a systemically acting anticholinergic-antihistaminic agent that readily crosses the bloodbrain barrier, has been studied in a limited fashion in OP. [4][5][6][7] This prior research suggests that DPH may be useful as an alternative or adjunctive therapy in OP. This investigation sought to evaluate the protective effects of DPH in a rat model of acute, severe OP.…”

mentioning

confidence: 99%

Diphenhydramine as a Protective Agent in a Rat Model of Acute, Lethal Organophosphate Poisoning

Bird

2002

Academic Emergency Medicine

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Objective: To evaluate the effects of diphenhydramine chloride (DPH) on mortality in a rat model of acute, severe organophosphate poisoning (OP). Methods: Wistar rats (n = 40) were randomized to pretreatment with either normal saline (controls), 5 mg/kg atropine, 3 mg/kg DPH, 15 mg/kg DPH, or 30 mg/kg DPH given as a single intramuscular injection 5 minutes prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). The primary endpoint was 10-minute survival. Survival at 24 hours was a secondary endpoint. Comparison of survival rates between groups was carried out by ANOVA and the Student-Newman-Keuls test. Results: Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts. In controls, fasciculations were followed by respiratory arrest within 10 minutes (0% survival). The rats receiving atropine pre-treatment exhibited similar fasciculations (nicotinic effects) without subsequent respiratory arrest, resulting in a significant improvement in survival (88%, p < 0.001). The DPH-treated rats exhibited a significant dose-dependent reduction in mortality, with the 3 mg/kg, 15 mg/kg, and 30 mg/kg groups demonstrating 0%, 25%, and 100% survival, respectively. There was no additional mortality between 10 minutes and 24 hours in any group. There was no significant difference in survival between the high-dose DPH and the atropine groups. Conclusions: Diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorvos exposure.

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Effect of diphenhydramine on organophosphorus insecticide toxicity in mice

Cited by 16 publications

References 11 publications

Acute Toxicity and Neurobehavioral Effects of Diphenhydramine in Chicks

Acute Toxicity and Neurobehavioral Effects of Diphenhydramine in Chicks

Comparative Pharmacology and Toxicology of Pharmaceuticals in the Environment: Diphenhydramine Protection of Diazinon Toxicity in Danio rerio but Not Daphnia magna

Diphenhydramine as a Protective Agent in a Rat Model of Acute, Lethal Organophosphate Poisoning

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