Kinetics and rat locomotor activity following cocaine and lidocaine administration.

Cocaine abuse is a widespread problem in the USA. Illicit cocaine is usually never found in pure form but is adulterated with other agents, among which are the local anesthetics such as lidocaine. Adulteration of cocaine with another active agent allows the potential for various drug-drug interactions to occur. The presence of an additional active agent in illicit cocaine samples can complicate the pharmacological and toxicological responses elicited and possibly the mode of emergency medical care thereafter. When studying drug interactions, both the kinetic and dynamic aspects of each agent must be considered. This study investigated the plasma time course and tissue distribution of cocaine and lidocaine alone and in combination following a 5 mg kg(-1) intravenous injection in rats. The plasma time course of cocaine and lidocaine in combination did not differ from that seen when each drug was alone. Tissue contents were without change when administered alone or in combination at 5, 10 and 15 min following treatment. However, rats treated with cocaine and lidocaine in combination had significantly greater locomotor activity initially than animals treated with cocaine alone. The results suggest that cocaine and lidocaine interact on a pharmacodynamic basis without a change in the drug level of each agent.

Decreased cocaine- and lidocaine-induced seizure response by dextromethorphan and DNQX in rat.

The present study investigated the effect of dextromethorphan and 6,7-dinitroquinoxaline-2,3-dione (DNQX) pre-treatment on the development of cocaine- and lidocaine-induced seizures. The dopaminergic action of cocaine was also studied. The NMDA antagonist dextromethorphan and the non-NMDA (AMPA/kainate) antagonist DNQX both significantly decreased the intensity of the seizure response to intravenous convulsant doses of cocaine and lidocaine individually (20 mg/kg) and in combination (5 mg/kg each). The incidence of seizures in rats receiving cocaine or lidocaine individually was significantly reduced by pre-treatment with dextromethorphan but not DNQX. Haloperidol did not have an effect on the incidence or intensity of seizures induced by cocaine or lidocaine, alone or in combination. The results suggest that local anesthetic-induced convulsive seizures are mediated by excitatory glutamate transmission through both NMDA and non-NMDA receptor systems.

Effect of sub-chronic cocaine and lidocaine exposure on the lymphoid tissues in neonatal rats.

Illicit cocaine varies in purity and is often adulterated with local anesthetics such as lidocaine. Chronic cocaine exposure is associated with immunological modulation in humans and animal models. The effect of sub-chronic oral exposure to cocaine (COC) and lidocaine (LIDO) alone and in combination on the lymphoid organs was assessed in neonatal rats. Lewis rat pups were orally administered saline (SAL), COC, LIDO or both drugs in combination, 20 mg/kg each, from birth to day 21. Statistically significant (P < 0.05) decreases in lymphocyte and total leukocyte levels as well as decreases in spleen weight were observed in pups treated with COC alone. LIDO alone did not affect these parameters in comparison to SAL treated controls. Rats receiving COC and LIDO did not display a significant reduction in spleen weight or in the blood cell populations studied. However, rats treated with COC and LIDO in combination had significantly decreased serum immunoglobulin M (IgM) concentration. Quantitative plasma and tissue analyses ascertained the concentrations and tissue disposition of each drug following oral administration. The results suggest that the effect of COC on the lymphoid tissues and white blood cell parameters is modified in the presence of LIDO in the developing rat.

Cocaine and lidocaine in combination are synergistic convulsants.

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.

Development and validation of a high-performance liquid chromatography method for the determination of cocaine, its metabolites and lidocaine.

Street cocaine varies in purity and is often adulterated with various compounds. Some of these additives, such as lidocaine, may increase the toxicity of cocaine. A new precise, accurate and sensitive reversed-phase high-performance liquid chromatography method for the determination of cocaine, its metabolites and lidocaine in plasma samples has been developed and validated. This assay employed a phosphate-buffered aqueous mobile phase (pH 6.0) with an organic component consisting of acetonitrile and methanol and a C-18 column as the stationary phase. Minimum detection limits were 1 ng ml-1 for cocaine, 2.5 ng ml-1 for ethylcocaine and 5 ng ml-1 for benzoylecgonine, norcocaine, norethylcocaine and lidocaine. Linearity was demonstrated over a broad range of concentrations in plasma, with good sensitivity for cocaine and cocaine derivatives.

Safety evaluation of benzophenone-3 after dermal administration in rats.

Benzophenone-3 (BZ-3) is a category 1 (over-the-counter) product approved by the US Food and Drug Administration (FDA) for use as a sunscreen agent in medicine, cosmetics, industry, and agriculture. This is due to its ability to absorb and dissipate ultraviolet light in a harmless manner, thus protecting human skin and products from UV irradiation. This study investigated the safety of BZ-3 after repeated administration. BZ-3 in ointment base was applied at a dose of 100 mg/kg body wt. twice daily, for 4 weeks to the skin of male Sprague-Dawley rats. Body weight, organ to body weight ratios, hematological, and clinical chemistry parameters were not effected. Pathological examination revealed no significant changes between control and treated animals. No gross external abnormalities were observed. Both in vivo and in vitro blood glutathione (GSH) levels were effected by BZ-3 treatment. However, after 60 min of incubation, a reversal of this effect was observed in the treatment group as blood GSH levels approached normal levels. Furthermore, investigation of GSH-reductase and peroxidase with time indicated an increase in GSH-reductase activity at 60 and 90 min with no effect on GSH-peroxidase. Pre-treatment with phenobarbital modulated the metabolic disposition of BZ-3. There was an increase in the formation of the hydroxy metabolites but not the O-dealkylated form. This study suggests that BZ-3 is not toxic to rats when applied dermally at a dose of 100 mg/kg body wt. for 4 weeks.