The effects of simultaneous atropine and labetalol administration on cardiovascular parameters during anticholinesterase poisoning in anaesthetized cat.

The effects of atropine administration during anticholinesterase poisoning on heart rate, blood pressure and electrocardiographic changes (ECG) were studied in the cat. Administration of atropine intravenously during anticholinesterase poisoning caused a significant increase in heart rate and blood pressure; ECG changes were also seen. The simultaneous intravenous administration of atropine and labetalol during anticholinesterase poisoning abolished the increase in blood pressure and heart rate; ECG readings remained normal. It is suggested that labetalol may be a useful adjuvant in the treatment of anticholinesterase poisoning especially in patients with compromised heart function.

[Thiol compounds in the combined therapy of prozerin poisonings]. / Tiolovye soedineniia v kombinirovannoi terapii otravlenii prozerinom.

The authors studied the protective action of dithiols (unithiol, dithiothreitol) and their combinations with atropine in proserine poisoning. With the use of the spatial-prospective plotting the antidote efficacy of dipyroxime, atropine, dithiothreitole, and their combinations was studied and compared. A new type of potentiation was discovered upon combined use of atropine, dipyroxime and dithiothreitol.

[Trial of cholinesterase reactivators as proserine antagonists]. / Ispytanie reaktivatorov kholinésterazy kak antagonistov prozerina.

HI-6 and TMB-4 were the most effective and safe of 7 cholinesterase reactivators tested as agents for the prophylaxis of proserine poisoning of male mice. The reactivator HI-6 strongly potentiated the prophylactic efficacy of a mixture of atropine and arpenal administered in the doses sufficient for the blockade of both the m- and h-cholinoreactive systems of mice. As demonstrated by experiments in vitro, HI-6 and TMB-4 did not reacivate proserine-inhibited cholinesterase. The natural anticholinesterase activity of HI-6 was negligible. Based on the correlation of the data obtained to the reported data indicating that HI-6 has a low ganglioblocking activity it is inferred that the direct effect on the receptor is of no importance for the potentiating effect. It is assumed that HI-6 modulates the cholinoreactive systems, which leads to a dramatic increase of the efficacy of cholinolytics.

Mechanism of the clonidine-induced protection against acetylcholinesterase inhibitor toxicity.

Clonidine, an alpha-2 adrenergic agonist can inhibit the release of acetylcholine from central and peripheral cholinergic neurons. This study was designed to examine the ability of clonidine to protect animals from the toxic manifestations of cholinesterase poisoning. Physostigmine, a central and peripheral cholinesterase inhibitor produced tremors, and at high doses death, by respiratory paralysis. Mice were injected with physostigmine at a dose (0.75 mg/kg) which evoked tremors in 100% and death in 90% of the animals. Clonidine pretreatment (0.3 mg/kg) increased the onset latency to tremor from 5 to 20 min, increased the onset latency to death from 12 to 24 min and increased the percentage of survivors to 50%. Yohimbine (1 mg/kg) reversed these protective effects of clonidine. The physostigmine-induced accumulation of forebrain and hindbrain acetylcholine also was reduced by 50% in both brain regions in clonidine-pretreated mice. Neostigmine, a selective peripheral cholinesterase inhibitor, induced respiratory paralysis which was not affected by clonidine pretreatment. These findings indicate that central cholinergic neurons involved in the regulation of respiration and fine motor control, but not peripheral motor neurons, are inhibited by clonidine acting on alpha receptors.