Physiological, biochemical and histological changes due to physostigmine in monkeys

Area of Science:

• Toxicology
• Pharmacology
• Neuroscience

Background:

• Organophosphorous (OP) compounds are highly toxic and require effective antidotes.
• Physostigmine (Phy), a reversible anticholinesterase, is a potential prophylactic agent against OP toxicity.

Purpose of the Study:

• To evaluate the physiological, biochemical, and histological effects of probable prophylactic doses of Physostigmine in monkeys.
• To determine a safe and effective dose of Phy for potential use in pretreatment regimens against nerve agents.

Main Methods:

• Monkeys were administered Physostigmine at doses of 50 and 100 micrograms/kg.
• Evaluated physiological parameters (cholinergic signs, heart rate, respiration, brain activity), clinico-chemical effects (blood gases, pH), and erythrocyte/plasma cholinesterase (ChE) activity.
• Histological examination of lung tissue was performed.

Main Results:

• The 100 micrograms/kg dose of Phy induced cholinergic signs (salivation, lacrymation, fasciculations), physiological changes (tachycardia, tachypnea, altered brain activity), and lung inflammation.
• The 50 micrograms/kg dose of Phy did not cause overt cholinergic signs but significantly inhibited plasma and erythrocyte ChE and increased rectal temperature.
• Both doses showed a fall in PO2, PCO2, and induced alkalosis.

Conclusions:

• Physostigmine at 50 micrograms/kg appears to be a safe, sign-free intramuscular dose for monkeys.
• This dose may be suitable for a pretreatment regimen against organophosphorous nerve agents.
• Further research is warranted to confirm the safety and efficacy in humans.