Effect of preceding physostigmine administration on neuromuscular transmission disturbances in rats caused by dichlorphos and phospholine.

The reported experiments were carried out on male Wistar rats. Under general anaesthesia with chloral hydrate in situ physiological preparations were made consisting of sciatic nerve and anterior tibialis muscle. Physostigmine was injected subcutaneously and was followed after from 15 to 60 minutes by intravenous injection of DDVP or phospholine. Physostigmine effect on the blockade of tetanic muscular contractions was studied after administration of these organophosphate inhibitors of acetylcholinesterase. At the same time, the effect of these substances on acetylcholinesterase was determined in the skeletal muscle. It was found that physostigmine in a dose of 125 microgram/kg protected the tibialis muscle against the development of blockade of tetanic response. The protective effect was greatest when the time between physostogmine injection and the subsequent administration of these organophosphate inhibitors was 30--40 minutes. In the same observation period the activity of AChE in the tibialis muscle of rats was found to be highest after physostigmine injection before administration of DDVP or phospholine.

Antiesterase activity of chlorphenvinphos and phospholine in certain rat tissues after administration by different routes.

The reported investigations were carried out on female Wistar rats receiving chlorphenvinphos and phospholine in doses equalling 3/4 LD50 onto the skin and intragastrically. the levels of acetylcholinesterase (AChE) were determined in the erythrocytes, liver and tibialis muscle and in three brain areas: pontomedullary area, hypothalamus and cerebral cortex. The activity of the enzyme was determined 15 and 30 minutes, and 3, 24 and 72 hours after poisoning. A high degree of AChE inhibition was observed in the brain after chlorphenvinphos poisoning (activity fall to 15--30%) and a slight decrease of AChE activity after administration of phospholine independently of the route. After oral poisoning with both preparations the AChE activity level in the erythrocytes was from about 27% to 31%, in the liver from 18 to 23%, and in the skeletal muscle from 51 to 54%, while with the transcutaneous route of poisoning these values were: 18--23%, 41--52%, and 36--48% respectively. A high degree of enzyme restoration was observed during 72 hours of observation. AChE activity was then 60--80% of the initial value.

Protective effect of some pyridinium salts on acetylcholinesterase against organophosphate inhibition.

The protective effect of ten new synthetized mono- and bis-pyridinium salts on acetylcholinesterase (AChE) against DFP, Chlorphenvinphos, DDVP, IPO 62 and IPO 63 inhibition in vitro and in mice i.p. was studied. Moreover, abolition of tetanic block of the tibialis anterior muscle in rats after intoxication with DDVP by these salts was tested. An increase of the therapeutic effect of atropine after DFP poisoning in mice and a rise of LD50 values from 1.4 (PAN-W-15) to 5.1 times (PAN-W-14) was noted. The effect of PAN-W-14 and PAN-W-18 after inhibition by other organophosphates was found to be highest in human erythrocytes in vitro. In addition, prophylactic administration of PAN-W-14 prevented the tetanic block of the muscle in situ after DDVP intoxication.

Histopathology, histochemistry and acetylcholinesterase activity after repetitive administration of fluostigmine to albino rat.

Histopathological, histochemical and biochemical investigations were performed on the brain, sciatic nerve, skeletal muscle, heart, liver and kidney of rats which were given 5% of LD50 dose of DFP for 10 days. A decrease in AChE activity, degeneration of neurons and necrotic changes in the nuclei of hypothalamus, degeneration of myelin sheaths in sciatic nerve, a decrease in succinic dehydrogenase activity in the myocardium, and a minimal decrease of acid phosphatase activity (AcPh) in the liver were found. The biochemical determination of AChE level indicated about 30% AChE activity in erythrocytes and tibialis muscle, and 40% in the brain 1 hr after the last dose of the inhibitor and 80% and 50% respectively on the 7th day after poisoning in relation to normal values.