Inhibitor Report for: Propaphos

The serum cholinesterase (ChE) isoenzyme patterns consist of 5 bands for normal beagle dogs. We examined the ChE isoenzyme patterns and ChE activities of 4 groups, each of which consisted of 4 dogs, given the organophosphate (OP) compounds fenthion (P = S type), isoxathion (P = S type), dichlorvos (P = O type) or propaphos (P = O type) po at 220, 75, 120 or 90 mg/kg respectively. Blood samples were collected for 30 d after the OP administrations. ChE isoenzyme bands 4 and 5 were inhibited 12 h after fenthion and isoxathion administration; dichlorvos and propaphos produced suppression of main bands 4 and 5 20 min after administration. This change was effective to differentiate the type of OP administered (P = S and P = O), while the main ChE isoenzyme bands of dog serum reflected inhibition of serum ChE activity.

The serum cholinesterase (ChE) isoenzyme in rats shows 6 bands after polyacrylamide gradient gel electrophoresis. The effects of organophosphates (fenthion, chlorpyrifos, diazinon, bromophos, propaphos, haloxon, and DFP) on serum ChE isoenzyme bands were studied in 32 male and 32 female 6-w-old Sprague-Dawley rats. Each organophosphate was randomly administered to 4 male and 4 female rats. Blood samples were collected from the abdominal aorta under halothane anesthesia 6 h after dosing. The isoenzyme patterns were determined simultaneously with erythrocyte and serum ChE activities. Changes were observed in all 6 bands of the serum ChE isoenzymes after administration of fenthion, chlorpyrifos and propaphos. Diazinon had no influence on band 6, and DFP and bromophos had no influence on band 5. Haloxon did not effect any of the serum ChE isoenzyme bands. Serum ChE was most suppressed by fenthion, followed by DFP, bromophos, chlorpyrifos, propaphos and diazinon in that order of effect. Serum ChE activity was not suppressed by haloxon. Erythrocyte ChE activity was suppressed by every organophosphate. This experiment demonstrated a correlation between the organophosphate suppression of serum ChE activity and the concentration of serum ChE isoenzyme band 6.

Stereoselectivity on sulfoxidation of propaphos (1, O,O-dipropyl O-4-methylthiophenyl phosphate, Kayaphos) into propaphos sulfoxide (2, O,O-dipropyl O-4-methylsulfinylphenyl phosphate) with German cockroach and biological activity of both enantiomers of 2 were examined. Metabolic 2 was analyzed by chiral HPLC on CHIRALCEL OA with hexane-propan-2-ol (9:1) to determine that the enantiomeric ratio of (R)s-(+) to (S)s-(-)-2 was 56:44. Both enantiomers of 2 were prepared by optical resolution with the same chiral HPLC. (-)-2 was about threefold more potent as an inhibitor of German cockroach and bovine erythrocyte acetylcholinesterases, whereas (+)-2 was twofold more insecticidal to German cockroach. There is little difference of toxicity to the house fly and the green rice leaf hopper between the enantiomers of 2..

The serum cholinesterase (ChE) isoenzyme patterns consist of 5 bands for normal beagle dogs. We examined the ChE isoenzyme patterns and ChE activities of 4 groups, each of which consisted of 4 dogs, given the organophosphate (OP) compounds fenthion (P = S type), isoxathion (P = S type), dichlorvos (P = O type) or propaphos (P = O type) po at 220, 75, 120 or 90 mg/kg respectively. Blood samples were collected for 30 d after the OP administrations. ChE isoenzyme bands 4 and 5 were inhibited 12 h after fenthion and isoxathion administration; dichlorvos and propaphos produced suppression of main bands 4 and 5 20 min after administration. This change was effective to differentiate the type of OP administered (P = S and P = O), while the main ChE isoenzyme bands of dog serum reflected inhibition of serum ChE activity.

The serum cholinesterase (ChE) isoenzyme in rats shows 6 bands after polyacrylamide gradient gel electrophoresis. The effects of organophosphates (fenthion, chlorpyrifos, diazinon, bromophos, propaphos, haloxon, and DFP) on serum ChE isoenzyme bands were studied in 32 male and 32 female 6-w-old Sprague-Dawley rats. Each organophosphate was randomly administered to 4 male and 4 female rats. Blood samples were collected from the abdominal aorta under halothane anesthesia 6 h after dosing. The isoenzyme patterns were determined simultaneously with erythrocyte and serum ChE activities. Changes were observed in all 6 bands of the serum ChE isoenzymes after administration of fenthion, chlorpyrifos and propaphos. Diazinon had no influence on band 6, and DFP and bromophos had no influence on band 5. Haloxon did not effect any of the serum ChE isoenzyme bands. Serum ChE was most suppressed by fenthion, followed by DFP, bromophos, chlorpyrifos, propaphos and diazinon in that order of effect. Serum ChE activity was not suppressed by haloxon. Erythrocyte ChE activity was suppressed by every organophosphate. This experiment demonstrated a correlation between the organophosphate suppression of serum ChE activity and the concentration of serum ChE isoenzyme band 6.

Stereoselectivity on sulfoxidation of propaphos (1, O,O-dipropyl O-4-methylthiophenyl phosphate, Kayaphos) into propaphos sulfoxide (2, O,O-dipropyl O-4-methylsulfinylphenyl phosphate) with German cockroach and biological activity of both enantiomers of 2 were examined. Metabolic 2 was analyzed by chiral HPLC on CHIRALCEL OA with hexane-propan-2-ol (9:1) to determine that the enantiomeric ratio of (R)s-(+) to (S)s-(-)-2 was 56:44. Both enantiomers of 2 were prepared by optical resolution with the same chiral HPLC. (-)-2 was about threefold more potent as an inhibitor of German cockroach and bovine erythrocyte acetylcholinesterases, whereas (+)-2 was twofold more insecticidal to German cockroach. There is little difference of toxicity to the house fly and the green rice leaf hopper between the enantiomers of 2..

The effect of 4-methylthiophenyl dipropylphosphate (propaphos, organophosphorus insecticide) and 2-sec-butylphenyl-N-methylcarbamate (BPMC, carbamate insecticide) on the sensitivity to the effects of acetylcholine (ACh), carbachol (CCH) and nicotine was investigated on guinea-pig isolated ilea and atria. The response of these tissues to ACh was significantly enhanced in the presence of propaphos (3.3 x 10(-7) M) or BPMC (4.5 x 10(-6) M), while that to CCH was unaffected. The repeated administration of propaphos (5 mg/kg/day, p.o.) for 7 days had no effect on the contractile responses of guinea-pig ilea to potassium chloride. The responses of ilea and atria to ACh and nicotine were markedly increased by the administration of propaphos, and the values of ED50 and ED80 for their responses were significantly decreased. On the other hand, the response to CCH was decreased as was demonstrated by a significant increase in these values. Pretreatment with BPMC (25 mg/kg/day p.o., 7 days) significantly reduced the alteration in the responsiveness of the tissues to ACh, CCH and nicotine produced by the propaphos administration. The activity of cholinesterase (ChE) declined by 50--70% in blood and tissues from propaphos-treated animals, and its inhibition was significnatly reduced by the pretreatment with PBMC to 30--40%. These results indicate that changes in synaptic ChE activity, as reflected by the changes in ChE activity of blood and tissues, may be responsible for the alteration in sensitivity of ilea and atria to cholinergic agents produced by the repeated administration of propaphos and for the antagonism by BPMC.