Effect of organophosphates on dopamine and muscarinic receptor binding in rat brain.
The effect of Soman, Sarin and Vx, known potent cholinesterase inhibitors, on the binding of several neurotransmitter receptors in various regions of brain was studied. Vx, exhibited considerable inhibition of binding of 3H-N-methylscopolamine (3H-NMS) to muscarinic receptors and of 3H-spiperone to dopamine D2 receptors in the striatum. 3H-NMS binding was 50% inhibited at 10(-6)M and 90% at 10(-3)M Vx. Inhibition of 3H-spiperone binding by Vx in striatum had an ID50 of 10(-5)M. KD of the treatment was affected more than Bmax. Binding inhibition of both 3H-NMS and 3H-spiperone in post-mortem brain of rats pre-treated with Vx confirmed the specificity of the organophosphates effect, since other organophosphates and ligands failed to show any activity.
Naseem
S M
SM
University of Maryland, School of Medicine, Baltimore 21201.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D019832:N-Methylscopolamine; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012524:Sarin / Q000494:pharmacology; D012602:Scopolamine Derivatives / Q000378:metabolism; D012999:Soman / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D019832:N-Methylscopolamine; D009946:Organothiophosphorus Compounds; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D012524:Sarin; D012602:Scopolamine Derivatives; D012999:Soman; D013134:Spiperone; C009680:VX-agent