title: Cocaine and lidocaine in combination are synergistic convulsants.
abstract: The abuse of cocaine has dramatically increased in the recent decade. Cocaine obtained on the illegal market is rarely found in pure form. Most often it is adulterated with various substances, especially other local anesthetics. Lidocaine is one of the most common local anesthetics employed for adulteration of illicit cocaine. Toxicity due to the simultaneous ingestion of cocaine and lidocaine has been reported. Acute toxicity to cocaine and other local anesthetics is manifested in central nervous system aberrations, such as seizures and convulsions. This study investigated the convulsant potency of cocaine and lidocaine alone and in combination. Rats were administered intravenous injections of 5 mg/kg or 20 mg/kg of cocaine or lidocaine alone and in combination in equal proportion. Seizure activity and intensity were evaluated. The plasma concentration and brain content of each agent was also determined at the time of toxicity. The administration of 5 mg/kg of each drug alone did not yield seizure activity. However, the concomitant administration of 5 mg/kg of both cocaine and lidocaine produced a seizure response nearly equal to that produced after administration of 20 mg/kg of cocaine alone. Diazepam pre-treatment successfully antagonized the seizures induced by cocaine and lidocaine and raised the seizure threshold dose for the combination treatment by approximately four fold. The results suggest that cocaine and lidocaine interact synergistically to increase seizure activity and that the nature of this response occurs in part through a depression of inhibitory neuronal transmission.
authors.affiliation: Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Barat
authors.forename: M S
authors.initials: MS
authors.lastname: Abdel-Rahman
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004357:Drug Synergism; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy*
chemical_list: D008012:Lidocaine; D003042:Cocaine