Prevention of organophosphate intoxication with presynaptic cholinergic blockers

doi:10.1016/0024-3205(94)90082-5

Life Sciences

Volume 55, Issue 1, 1994, Pages 69-75

https://doi.org/10.1016/0024-3205(94)90082-5 Get rights and content

Abstract

In Vivo cardiovascular neuromuscular preparation of rats was used to study the prophylaxis and mechanism of diisopropyl fluorophosphate (DFP) intoxication by presynaptic cholinolytic agents (ganglionic blocking agents), including hexamethonium, trimethaphan and mecamylamine. The lethal action of DFP was partially or completely prevented by pretreatment of rats with hexamethonium (10 mg/kg), trimethaphan (80 mg/kg) and mecamylamine (30 mg/kg). Combined use of these drugs with 2-PAM (100 mg/kg) improved further the prophylaxis of DFP lethality. The mechanism of prophylaxis could be due to the reduction of acetylcholine turnover and accumulation at the synaptic cleft as hemicholinium prevented the DFP intoxication efficiently. In all cases, DFP caused cardiovascular suppression before neuromuscular blockade indicating that the cardiovascular system is much more sensitive than the neuromuscular junction to DFP intoxication.

References (7)

G.C.Y. Chiou et al.
Fund. Appl. Toxicol.
(1986)
J.J. Gordon et al.
Toxicol. Appl. Pharmacol.
(1978)
G.C.Y. Chiou
Eur. J. Pharmacol.
(1970)

There are more references available in the full text version of this article.

Cited by (5)

Protective effect induced by atropine, carbamates, and 2-pyridine aldoxime methoiodide Artemia salina larvae exposed to fonofos and phosphamidon
2007, Ecotoxicology and Environmental Safety
The acute toxicity of fonofos and phosphamidon on three age classes of Artemia salina was evaluated. An increase in toxicity of these organophosphorous (OP) insecticides was found following longer development of A. salina. The effects of pretreatment with the nonselective muscarinic antagonist atropine, the two reversible acetylcholinesterease inhibitors physostigmine and pyridostigmine, and the cholinesterase-reactivating oxime 2-pyridine aldoxime methoiodide (2-PAM), as individual and combined pretreatments, on OP-induced lethality in 24 h Artemia were also investigated. The lethal action of both OP insecticides was prevented by pretreatment of 24 h Artemia with atropine and 2-PAM, while physostigmine proved ineffective against intoxication with both OP insecticides and pyridostigmine exhibited a low synergic effect. In both cases, the inhibitory effects of combinations of atropine (10⁻⁵ M) plus 2-PAM were greater than those elicited by either drug alone, with the maximum protection afforded being 100%. Combined pretreatment of atropine (10⁻⁵ M) plus physostigmine practically abolished the lethal effects induced by both insecticides. Pretreatment with 2-PAM (10⁻⁶ M) plus physostigmine afforded maximal protection of 100% and 76% on the lethality induced by fonofos and phosphamidon, respectively. The data obtained suggest that the combination of atropine plus 2-PAM or physostigmine and the combined pretreatment of 2-PAM plus physostigmine are effective in the prevention of the lethal effects induced by fonofos and phosphamidon in A. salina larvae.
Bicyclic Systems with Ring Junction Sulfur, Selenium, or Tellurium Atoms
1996, Comprehensive Heterocyclic Chemistry II: A Review of the Literature 1982-1995
Central Mechanisms of Seizures and Lethality Following Anticholinesterase Pesticide Exposure
2011, Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology
The use of carbamates, atropine, and 2-pyridine aldoxime methoiodide in the protection of Artemia salina against poisoning by carbophenothion
2001, Environmental Toxicology and Chemistry
Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae
1996, Archives of Environmental Contamination and Toxicology

View full text

Prevention of organophosphate intoxication with presynaptic cholinergic blockers

Abstract

Fund. Appl. Toxicol.

Toxicol. Appl. Pharmacol.

Eur. J. Pharmacol.