Effects of anticholinergic-antiparkinsonian drugs on striatal neurotransmitter levels of rats intoxicated with soman.
Antimuscarinic drugs possessing antiparkinson activity that were effective in preventing convulsions induced by the organophosphorus cholinesterase (ChE) inhibitor soman were studied for their effects on spinal cord ChE activity and striatal levels of acetylcholine (ACh) and catecholamines in soman-intoxicated rats. Either biperiden (BPR) or trihexyphenidyl (THP) was administered to rats at an anticonvulsant dose (0.125 mg/kg, IM) in the presence or absence of soman (100 micrograms/kg, SC). The time course (up to 2 h) for ChE activity and levels of ACh and catecholamines were measured after soman, BPR, THP, soman and BPR, or soman and THP treatment. Soman rapidly inhibited ChE activity (65-75%; 15-120 min) and increased ACh levels (35%; at 30 min). It did not affect norepinephrine or dopamine (DA), but elevated at later time points (60-120 min) levels of the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), thus indicating increased DA turnover. BPR and THP alone reduced striatal ACh level from control, but did not affect any other neurochemical parameters studied. THP and BPR each reversed the effects of soman on DOPAC and HVA levels, but neither affected ChE activity nor ACh level induced by soman. Thus, our findings suggest that the anticonvulsant effects of BPR and THP in soman poisoning may be attributed to their earlier reported muscarinic receptor blocking properties.
Shih
T M
TM
Pharmacology Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Capacio
B R
BR
Cook
L A
LA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001712:Biperiden / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012999:Soman / Q000633:toxicity*; D013116:Spinal Cord / Q000201:enzymology; D014282:Trihexyphenidyl / Q000494:pharmacology
D000978:Antiparkinson Agents; D002395:Catecholamines; D018377:Neurotransmitter Agents; D010276:Parasympatholytics; D001712:Biperiden; D014282:Trihexyphenidyl; D012999:Soman; D002802:Cholinesterases; D000109:Acetylcholine