OBJECTIVETo examine the therapeutic effect of combined use of obidoxime and atropine with artificial ventilation on respiratory muscle paralysis caused by omethoate poisoning in rats.

METHODSRats were exposed to 2 times the dose of LD50 omethoate and treated with atropine (10 mg/kg) to counteract cholinergic symptoms. When the rats' respiratory frequency became slower and breathed with difficulty, the trachea intubation and artificial ventilation was carried out. The rats in group A were continuously treated with atropine. The dose of obidoxime for Group B, C and D were 8, 15, 20 mg/kg respectively, given at the same time as artificial ventilation and 1, 2, 3 hours later. The doses of atropine was reduced to 1/3 - 2/3 of the first dose so as to maintain the rats atropinized. If the rat survival was beyond 60 minutes after withdrawal of artificial ventilation, the combined treatment was considered successful. The function of isolated phrenic diaphragm of the rats was observed with MS-302 physiological and pharmacological analysis instrument.

RESULTSNone of the rats in Group A was successful after withdrawal from artificial ventilation and the function of phrenic diaphragm appeared poor; whereas > 80% of the rats in B, C, D Group were successful after withdrawal from artificial ventilation in 3 h and the function of phrenic diaphragm remained well. The survival rate in B, C and D groups were higher after withdrawal from artificial ventilation than that in Group A(P < 0.01). The function of phrenic diaphragm in Group B, C and D were gradually decreased after ACh was added into the container.

CONCLUSIONSCombined use of suitable dose of obidoxime and atropine with artificial ventilation for respiratory muscle paralysis caused by omethoate poisoning could promote the recovery of diaphragm function and reduce the death rate in poisoned rats.

Animals ; Atropine ; administration & dosage ; Dimethoate ; analogs & derivatives ; poisoning ; Drug Therapy, Combination ; Obidoxime Chloride ; administration & dosage ; Rats ; Respiration, Artificial ; Respiratory Paralysis ; drug therapy

OBJECTIVEInhibition of acetylcholinesterase (AChE) in human brain caused by phoxim or phoxim oxon, their reactivation with oxime and aging of phosphorylated AChE were studied and compared in vitro.

METHODSMicro-colorispectrophotometric assay was used to determine the activity of AChE.

RESULTSThe pI(50) of inhibition of AChE in human brain by phoxim and phoxim oxon were 5.39 and 5.77, respectively, whereas the pI(90) were 4.60 and 5.00, respectively. The reactivation rate of 0.1 mmol/L of pralidoxime (2-PAM), obidoxime (LüH(6)), trimedoxime (TMB-4) and pyramidoxime (HI-6) for phoxim-inhibited AChE in human brain was 65%, 97%, 91% and 56%, respectively, and their reactivation rate for phoxim oxon-inhibited AChE in human brain was 97%, 87%, 99% and 89%, respectively. The optimal reactivator for phoxim and phoxim oxon-inhibited AChEs was LüH(6) and TMB-4, respectively. The half aging time of phoxim and phoxim oxon inhibited phosphorylated AChEs were 39 and 28 hours, respectively, and the 99% aging time were 256 and 186 hours, respectively.

CONCLUSIONSLüH(6) or TMB-4 should be used at the earlier as possible after poisoning with phoxim and phoxim oxon, and the reactivator should be consecutively used for more than seven days, even after their acute symptoms have been well controlled.

Acetylcholinesterase ; metabolism ; Brain ; drug effects ; enzymology ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterase Reactivators ; pharmacology ; Enzyme Stability ; Humans ; In Vitro Techniques ; Obidoxime Chloride ; pharmacology ; Organothiophosphorus Compounds ; pharmacology ; Oximes ; pharmacology ; Paraoxon ; pharmacology ; Pralidoxime Compounds ; pharmacology ; Time Factors ; Trimedoxime ; pharmacology