Title: Pharmacological modification of DDT-induced tremor and hyperthermia in rats: distributional factors.

Authors: Herr, D W; Hong, J S; Chen, P; Tilson, H A; Harry, G J

Published In Psychopharmacology (Berl), (1986)

Abstract: Pretreatment of rats with hydantoin (75 mg/kg, PO, an anticonvulsant), trihexyphenidyl (10 mg/kg, SC, a muscarinic cholinergic antagonist), or piperonyl butoxide (500 mg/kg, PO, a metabolic inhibitor) had no effect on the whole blood or brain tissue levels of orally administered DDT (75 mg/kg) or its metabolites DDD and DDE. Hydantoin and piperonyl butoxide decreased DDT-induced tremor and hyperthermia due to DDT when measured 12 h after DDT exposure, while trihexyphenidyl augmented some components of DDT-induced tremor. Additional experiments found that pretreatment with piperonyl butoxide increased tremor due to permethrin exposure (120 mg/kg, PO), while having no effect on tremor due to chlordecone administration (60 mg/kg, IP). Pretreatment with ellipticine (30 mg/kg, IP, a metabolic inhibitor) also decreased tremor 12 h after DDT exposure. The effects of piperonyl butoxide and ellipticine on DDT-induced tremor are postulated to occur through direct actions of these compounds on nerve or muscle tissue. Hydantoin-induced attenuation of DDT-induced neurotoxicity may be due to the ability of hydantoin to block repetitive firing of nerves by binding to the inactivation gates of sodium.

PubMed ID: 3088650

MeSH Terms: Animals; Brain Chemistry/drug effects; DDT/administration & dosage; DDT/analysis; DDT/toxicity*; Drug Interactions; Fever/chemically induced*; Hydantoins/administration & dosage; Male; Piperonyl Butoxide/administration & dosage; Rats; Rats, Inbred F344; Tremor/chemically induced*; Trihexyphenidyl/administration & dosage