Department of Veterinary Pharmacology and Toxicology, Mardras Veterinary College, Chennai-600007
A remarkable increase in the utilization of organophosphorus compounds (OPC) has created considerable concern over their toxic effects comprising motor, behavioural and autonomic symptoms, which are related to the inhibition of the enzyme acetylcholinesterase (AChE) in the cortex, striatum, hippocampus, hypothalamus and brainstem regions of the central nervous system. This was considered to be the main mode of action for a long time. Later it was found that OPC also exhibits non-cholinergic mechanisms involving noradrenaline (NA), dopamine (DA) and 5- hydroxytyptamine (5-HT). Some of the symptoms of OPC intoxication such as tremors have been related to the dopaminergic system, and therefore therapy must take into account not only cholinergic manifestations, but also other neurotransmitter alterations.
With these in mind, the present study was undertaken to find out the effects of phosphamidon (PM), an OPC administered alone and after pretreatment with domaminergic agonist drug bromocriptine, and an anticholinergic drug, on the DA levels in four discrete areas of the brain of rat, and to identify the correlation with toxic symptoms.
It was found that PM caused significant reduction of DA levels in the different areas of brain with resultant autonomic effects. Both DA level and autonomic effects of PM were reversed by atropine, and while bromocriptine did not influence the depressed DA level owing to its protective action, it may be combined with atropine for possible enhanced effects.
