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Pyrenebutyl-methylphosphonofluoridate: a fluorescent anti-cholinesterase in vivo
Abstract:
In vivo properties of pyrenebutyl-methylphosphonofluoridate (PBMPF) have been studied. The LD50 (i.v.) for mice was 15 mg/kg and toxic symptoms were typical of cholinesterase (ChE) inhibition but central signs were absent. After intraventricular injection of PBPMPF in unanaesthetized rabbits, continued walking in bizarre circular fashion together with peripheral vascular dilation and tachypnoea were observed. Recovery occurred 3 h post-injection. Fluorescent particles of unabsorbed material juxtaposed on lining ependyma were observed up to 14 days of administration. In addition, a large number of hippocampal cells showed vivid fluorescence, particularly in the cytoplasm, which was attributed to ChE inhibition. It is concluded that PBMPF seems promising as an organophosphate marker of nerve cells.
Insights
Pyrenebutyl-methylphosphonofluoridate (PBMPF) shows potential as an organophosphate marker for nerve cells. Studies in mice and rabbits revealed cholinesterase inhibition and unique cellular fluorescence, indicating its utility.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Organophosphates are known cholinesterase inhibitors.
- Developing specific markers for nerve cell activity is crucial in neuroscience.
Purpose of the Study:
- To investigate the in vivo properties and potential of pyrenebutyl-methylphosphonofluoridate (PBMPF) as a marker for nerve cells.
- To evaluate the toxicological effects and distribution of PBMPF in animal models.
Main Methods:
- Determined the LD50 (intravenous) in mice.
- Administered PBMPF intraventricularly in unanaesthetized rabbits.
- Observed toxic symptoms, recovery times, and analyzed cellular fluorescence using microscopy.
Main Results:
- The LD50 (i.v.) for mice was 15 mg/kg, with symptoms typical of cholinesterase (ChE) inhibition but no central signs.
- Rabbits exhibited circular walking, peripheral vascular dilation, and tachypnoea after injection, with recovery in 3 hours.
- Fluorescent particles were observed on ependyma for up to 14 days, and hippocampal cells showed vivid cytoplasmic fluorescence attributed to ChE inhibition.
Conclusions:
- PBMPF exhibits properties consistent with cholinesterase inhibition.
- The observed fluorescence in hippocampal cells suggests PBMPF's potential as a marker for nerve cells.
- PBMPF warrants further investigation as a novel organophosphate marker for neuronal activity.
