Effects of HI-6 and pralidoxime on neuronal RNA in thalamic cholinergic sites.
Quantitative azure B-RNA cytophotometry was employed to compare effects of the oximes HI-6 and pralidoxime (2-PAM) to those of atropine sulfate (AS) on neuronal RNA metabolism in the thalamic ventrobasal nuclear complex (VBC) and nucleus reticularis (NR). The ability of these compounds to mitigate soman (pinacolyl methylphosphonofluoridate)-induced neuronal RNA alterations (i.e., VBC-RNA depletion/NR-RNA elevation) in these muscarinic cholinergic sites was also determined. Generally, HI-6 (125 mg/kg, i.p.) and 2-PAM (43.2 mg/kg, i.m.) elicited similar patterns of neuronal RNA changes, i.e., diminution of VBC-RNA and NR-RNA with oximes alone; partial amelioration of soman (1.5 LD50, s.c.)-induced VBC-RNA loss; and slight or no effect on soman induced NR-RNA accumulation. HI-6 produced more severe RNA reduction than 2-PAM in both brain regions of non-poisoned rats, whereas 2-PAM was more effective in reversing the effects of soman in these two regions. The muscarinic antagonist, AS, also produced VBC-RNA depletion and partially counteracted the VBC-RNA loss in soman intoxicated rats. Unlike the oximes, however, AS resulted in NR-RNA accumulation and it also antagonized soman induced NR-RNA elevation. Neither oxime reactivated soman inhibited brain acetylcholinesterase but HI-6 did reactivate appreciable plasma cholinesterase. The overall data suggest that HI-6 and 2-PAM do exert pharmacologic actions on cholinergic neurons in the rat CNS. However, the greater effectiveness of HI-6 over 2-PAM in countering lethal actions of soman does not appear to be correlated with oxime mediated restoration of neuronal RNA levels in these two cholinergic regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
L J
LJ
Doebler
J A
JA
Anthony
A
A
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D003342:Corpus Striatum / Q000201:enzymology; D008297:Male; D010091:Oximes; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012313:RNA / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000037:antagonists & inhibitors*; D013787:Thalamic Nuclei / Q000187:drug effects*
D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D012313:RNA; D012999:Soman; D002802:Cholinesterases; C022870:asoxime chloride; C028797:pralidoxime