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Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration
A K Agarwal1, A Sankaranarayanan, P L Sharma
1Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh.
Abstract:
Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of LD50 given ip), produced several autonomic, neurological and behavioral effects in mice with peak effects being at 15 min. Similar dose in rats also abolished conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of these effects. This suggests that phosphamidon toxicity involves the central cholinergic, adrenergic, serotonergic and GABAergic systems in addition to peripheral cholinergic effects.
Insights
Phosphamidon insecticide causes autonomic, neurological, and behavioral effects in rodents. Pre-treatment with various drugs suggests toxicity involves central cholinergic, adrenergic, serotonergic, and GABAergic systems.
Area of Science:
- Toxicology
- Neuroscience
- Pharmacology
Background:
- Phosphamidon is a systemic organophosphate insecticide.
- Organophosphates are known for their neurotoxic effects.
Purpose of the Study:
- To investigate the autonomic, neurological, and behavioral effects of phosphamidon in mice and rats.
- To explore the neurochemical systems involved in phosphamidon toxicity.
Main Methods:
- Administration of phosphamidon (1.4 mg/kg, 1/4th LD50 ip) to mice and rats.
- Observation of autonomic, neurological, and behavioral effects.
- Assessment of conditioned avoidance response in rats.
- Evaluation of protective effects of pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine, and thiosemicarbazide.
Main Results:
- Phosphamidon induced significant autonomic, neurological, and behavioral effects in mice, peaking at 15 minutes.
- A similar dose abolished the conditioned avoidance response in rats.
- Pre-treatment with various agents partially or fully reduced these phosphamidon-induced effects.
Conclusions:
- Phosphamidon toxicity in rodents involves multiple central neurotransmitter systems.
- The observed effects suggest involvement of central cholinergic, adrenergic, serotonergic, and GABAergic systems.
- Peripheral cholinergic mechanisms also contribute to phosphamidon toxicity.