Diazepam protects against the enhanced toxicity of cocaine adulterated with atropine.
We examined the toxicity of cocatropine (cocaine/atropine mixture) and the therapeutic potential of diazepam on some behavioral and physiological parameters in rats. Atropine (20 and 60 mg/kg) or cocaine (40 mg/kg) alone did not induce any seizure or death, but the combination significantly increased both, after both acute and binge treatment. There was a significant increase of EEG mean total spectral power in cocatropine- in comparison with cocaine-treated animals. Hyperlocomotion was observed in non-seizuring rats treated with cocaine or cocatropine. Cocaine, atropine 60, and cocatropine (40 + 20 and 40 + 60) all induced hyperthermic effects in non-seizuring rats, while cocatropine (40 + 60)-seizuring animals had hypothermia. An initial hypertensive and tachycardiac effect within 15 min was followed by a secondary fall in the cocatropine (40 + 60) group. Cocatropine toxicity was partially or fully reversed by diazepam (5 mg/kg), given intraperitoneally after the first seizure. The present findings provide, for the first time, details of a synergistic toxic effect of the cocaine/atropine mixture and of the potential of diazepam for treating cocatropine-related hospital emergencies.
Braida
Daniela
D
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy.
Zani
Alessia
A
Capurro
Valeria
V
Rossoni
Giuseppe
G
Pegorini
Simona
S
Gori
Enzo
E
Sala
Mariaelvina
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001285:Atropine / Q000008:administration & dosage / Q000633:toxicity*; D001831:Body Temperature / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D003975:Diazepam / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004569:Electroencephalography; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010276:Parasympatholytics / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D000927:Anticonvulsants; D018765:Dopamine Uptake Inhibitors; D010276:Parasympatholytics; D001285:Atropine; D003042:Cocaine; D003975:Diazepam