Role of central biogenic amines on the protection afforded by clonidine against the toxicity of soman, an irreversible cholinesterase inhibitor.
Studies in our laboratory have demonstrated that alpha 2-adrenergic agonists such as clonidine offer protection against the toxicity caused by cholinesterase inhibitors such as soman. Experiments were designed to determine whether central catecholaminergic systems are implicated in the toxic and lethal manifestations of soman toxicity and whether the protection afforded by clonidine involves such pathways. Clonidine pretreatment resulted in a significant degree of protection from the lethal effects of soman in the mouse. Depletion of brain catecholamines did not alter soman-induced lethality or behavioral toxicity. Furthermore, catecholamine depletion was not effective in blocking clonidine-induced protection against soman toxicity. In contrast, elevation of brain catecholamines using the monoamine oxidase inhibitor, pargyline, resulted in significant protection against soman toxicity which was additive with that of clonidine.
Buccafusco
J J
JJ
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
Aronstam
R S
RS
Graham
J H
JH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry; D002395:Catecholamines / Q000172:deficiency* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D051379:Mice; D010293:Pargyline / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D012999:Soman / Q000037:antagonists & inhibitors / Q000633:toxicity*
D002395:Catecholamines; D012110:Reserpine; D012999:Soman; D010293:Pargyline; D003000:Clonidine