Arteether: risks of two-week administration in Macaca mulatta

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Arteether is an antimalarial drug.
• Neurotoxicity is a potential side effect of drug treatments.
• Understanding arteether's neurotoxic potential is crucial for its safe use.

Purpose of the Study:

• To investigate the neuroanatomical and neuropathological effects of arteether in male rhesus monkeys.
• To determine the dose-dependency and duration-dependency of arteether-induced neurotoxicity.
• To identify specific brain regions affected by arteether administration.

Main Methods:

• Male rhesus monkeys were administered daily doses of arteether (8, 16, or 24 mg/kg/day) for 7 or 14 days.
• Control groups received the vehicle (sesame oil) alone.
• Neurologic signs were monitored, and post-mortem examination included light microscopy of stained brain sections.

Main Results:

• Fourteen-day treatment with arteether resulted in dose-dependent brainstem injury, most severe at 24 mg/kg/day.
• Affected brainstem nuclei included the reticular formation, vestibular nuclei, and auditory system nuclei.
• Seven-day treatment showed no significant neuropathological findings, suggesting a duration-dependent effect.

Conclusions:

• Arteether induces significant brainstem neurotoxicity in rhesus monkeys following 14 days of administration.
• The observed neurotoxicity is dose-dependent, with higher doses leading to more severe injury.
• Shorter treatment durations (7 days) did not produce detectable neuropathological changes in the brainstem.