Depressor effects, drug concentration and cholinesterase activities in the brain after administration of paraoxon in the cat.
After simultaneous administration of paraoxon into both the left and right vertebral artery (4-8 micrograms) or into a femoral vein (150-550 micrograms.kg-1) of the anaesthetized cat, dose-dependent drug concentrations are measured in various brain regions. These amounts induce inhibition of brain acetylcholinesterase activity and dose-dependent depressor effects. Although paraoxon is rapidly eliminated from the CNS, enzyme activity remains at a low level. After central application of paraoxon into both vertebral arteries no detectable amounts are found in the hypothalamus and acetylcholinesterase activity in that brain region is not or only slightly affected. Curves representing the relationship between the decrease in blood pressure and the concentration of paraoxon or enzyme inhibition in the medulla oblongata are steep. Also, a steep dose-response curve for the depressor response to paraoxon is found. A reduction of brain enzyme activity to about 35% has no influence on blood pressure. However, inhibition by 65-100% induces dose-dependent depressor effects. The results support earlier findings that the depressor response to paraoxon is mediated by a central mechanism. This site of action is probably located within the medulla oblongata region.
D000110:Acetylcholinesterase / Q000032:analysis*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D010261:Paraoxon / Q000378:metabolism / Q000494:pharmacology*
D000110:Acetylcholinesterase; D010261:Paraoxon