In vivo dose response relationship between physostigmine and cholinesterase activity in RBC and tissues of rats.
Dose response of physostigmine (Phy) was studied in rat using various doses (25-500 micrograms/kg i.m.). Rats were sacrificed 15 min after Phy administration. Blood and tissues were analyzed for ChE activity by radiometric method and Phy concentration by HPLC method. A comparison of ChE values in different tissues of rats indicated that ChE activity was highest in brain (7.11 mumol/min/g) and least in diaphragm (0.67 mumol/min/g). The enzyme activity was eleven times more in brain as compared to diaphragm. Phy produced a dose-dependent inhibition of ChE in RBC (18-42%), brain (23-35%) and diaphragm (25-35%) from 50 to 200 micrograms/kg, then ChE inhibition was plateaued from 200 to 500 micrograms/kg in these tissues. A dose related ChE inhibition was seen in heart (16-50%) and thigh muscle (8-53%) from 50 to 500 micrograms/kg. Phy concentration increased linearly from 50 to 400 micrograms/kg in plasma, brain, heart and thigh muscle. These results indicate that ChE inhibition is linear up to 200 micrograms/kg in RBC, 150 micrograms/kg in brain and 300 micrograms/kg in heart. This linearity is not consistent in other tissues.
Somani
S M
SM
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-9230.
Dube
S N
SN
D000818:Animals; D001921:Brain / Q000201:enzymology; D002802:Cholinesterases / Q000378:metabolism*; D003964:Diaphragm / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010830:Physostigmine; D002802:Cholinesterases