Toxicity study of continuous administration of physostigmine salicylate.
The present study demonstrates that continuous administration with physostigmine salicylate (0.12 or 0.24 mg/kg/hr via mini-osmotic pumps) induces toxicities (e.g., body weight loss, decreased water consumption, tremors, decreased body temperatures, mortality) in guinea pigs. Both blood and brain cholinesterase activity is inhibited dose-dependently by physostigmine salicylate. The signs of toxicity in the guinea pigs which received the low dose appeared within 2 or 3 days and then the animals recovered, while toxic signs in the guinea pigs treated with the high dose of the drug persisted throughout the experiments. The study further shows that continuous administration of physostigmine salicylate also caused down-regulation of muscarinic receptors in the striata of the guinea pigs.
Lim
D K
DK
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Ito
Y
Y
Stewart
T
T
Hoskins
B
B
Ho
I K
IK
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D006168:Guinea Pigs; D007260:Infusion Pumps; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011976:Receptors, Muscarinic / Q000187:drug effects; D014202:Tremor / Q000139:chemically induced
D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; C026718:physostigmine salicylate; D010830:Physostigmine; D000110:Acetylcholinesterase