Diazepam inhibits organophosphate-induced central respiratory depression

Acad Emerg Med. 2003 Dec;10(12):1303-6. doi: 10.1111/j.1553-2712.2003.tb00001.x.


Objectives: Current evidence suggests that mortality from acute organophosphate (OP) poisoning is partially mediated through central nervous system (CNS) respiratory center depression (CRD). However, the exact mechanism of OP-induced CRD is unknown. In these studies, the authors investigated the hypothesis that OP-induced CRD is the result of overstimulation of CNS respiratory centers.

Methods: Wistar rats received prophylaxis with either normal saline (controls), atropine, the peripherally acting anticholinergics glycopyrrolate (GLYC), ipratropium bromide (IB), or the CNS respiratory center attenuator diazepam. To determine if a dual CNS/peripheral cholinergic mechanism is responsible for animal death, two additional groups received combination treatment with diazepam plus either IB or GLYC. All treatments were completed 5 minutes before OP with subcutaneous dichlorvos. Differences in 10-minute and 24-hour mortality were assessed by the Fisher exact test.

Results: Dichlorvos poisoning resulted in profound fasciculations without obvious seizure in all cohorts. In controls and animals treated with peripherally acting anticholinergics, fasciculations were followed by sedation and respiratory arrest (0% 10-minute survival in all cohorts). In contrast, pretreatment with either atropine or diazepam significantly improved 10-minute survival (100% and 44%, respectively). Although GLYC or IB afforded no protection when given alone, when delivered in conjunction with diazepam, the combination significantly improved survival (both groups 88% at 24 hours), suggesting a dual CNS/pulmonary muscarinic mechanism of lethality.

Conclusions: The central respiratory depressant diazepam paradoxically attenuates organophosphate-induced respiratory depression, and when combined with peripherally acting anticholinergic agents, reduces mortality in a rat model of severe acute OP poisoning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diazepam / therapeutic use*
  • Insecticides / toxicity*
  • Models, Animal
  • Muscle Relaxants, Central / therapeutic use*
  • Organophosphorus Compounds*
  • Prospective Studies
  • Rats
  • Rats, Wistar
  • Respiratory Insufficiency / chemically induced
  • Respiratory Insufficiency / drug therapy*
  • Respiratory Insufficiency / mortality


  • Insecticides
  • Muscle Relaxants, Central
  • Organophosphorus Compounds
  • Diazepam