Effects of inhibitors of acetylcholine synthesis on brain acetylcholine and survival in soman-intoxicated animals.
The effects of hemicholinium-3 (HC-3) or 4-(l-naphthylvinyl)pyridine (4-NVP) alone and together with cholinolytics and/or cholinesterase inhibitors on brain acetylcholine (ACh) levels and survival were studied. Intracerebroventricular (ICVT) injection of 10 micrograms HC-3 280 min before euthanasia by microwave irradiation reduced rat cerebral ACh levels from 28.4 to 5.4 nmoles ACh/g wet tissue. In rats pretreated with HC-3 alone or with other pretreatment drugs prior to giving up to 2.7 LD50 of soman, iv, cerebral ACh levels increased very little, but in animals not receiving HC-3, brain ACh levels increased to 67.1 nmoles. Treatment of unpoisoned rats with 4-NVP resulted in a significant (26%) reduction in ACh. The inclusion of atropine with 4-NVP caused sign-free doses of physostigmine to produce toxic signs in rabbits and did not enhance the efficacy of carbamate pretreatment against soman. Pretreatment of rabbits with pyridostigmine and atropine methyl nitrate (AMN) failed to provide any protection against soman, but when HC-3, ICVT, was included with those drugs, the protective ratio (PR), against soman was increased excess ACh is a primary lesion in organophosphorus anticholinesterase intoxication and that the central nervous system is quite sensitive to excesses of ACh.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006426:Hemicholinium 3 / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009286:Naphthylvinylpyridine / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000494:pharmacology*
D009943:Organophosphorus Compounds; D011725:Pyridines; D009286:Naphthylvinylpyridine; D006426:Hemicholinium 3; D001285:Atropine; D012999:Soman; D011729:Pyridostigmine Bromide; D000109:Acetylcholine