Biomedical subjects

L Virag

Publications and source records attributed to L Virag.

4 recordsLinked to original sources

PubMed1996

Determination of cocaine, norcocaine, benzoylecgonine and ecgonine methyl ester in rat plasma by high-performance liquid chromatography with ultraviolet detection.

An isocratic high-performance liquid chromatographic method with ultraviolet detection at 235 nm is described for the determination of cocaine and its metabolites benzoylecgonine, norcocaine and ecgonine methyl ester in rat plasma, collected during toxicity studies. Following simultaneous solid-phase extraction of all analytes and the internal standard tropacocaine, cocaine, benzoylecgonine and norcocaine were separated on a C18 column. Ecgonine methyl ester and cocaine were separated on coupled cyanopropyl and silica columns, following derivatization of ecgonine methyl ester to p-fluorococaine. The extraction efficiencies of these compounds from plasma ranged from 78 to 87%, while the limits of detection ranged from 35 to 90 ng/ml. The assay was linear from 300 to 5000 ng/ml, and the within-day precision 2 to 8% over this concentration range.

Animals↗

PubMed1996

Alpha-2 adrenoceptor agonists decrease cyclic guanosine 3',5'-monophosphate in the mouse brain.

BACKGROUND: In the central nervous system neurotransmitters, drugs or conditions that excite increase cyclic guanosine 3',5'-monophosphate (cGMP), an effect mediated by the neuromodulator nitric oxide, whereas those that sedate decrease cGMP. Volatile anesthetics were shown to decrease cerebellar cGMP, an effect that correlates with their anesthetic and anticonvulsant effect. Because alpha-2 adrenoceptor agonists have anesthetic properties, the role of the nitric oxide-cGMP pathway in the action of the alpha-2 adrenoceptor agonists clonidine and dexmedetomidine was investigated. METHODS: Groups of mice were given, intraperitoneally, one dose of either 30-600 micrograms/kg clonidine, or 3-300 micrograms/kg D-medetomidine (dexmedetomidine) or L-medetomidine. The alpha-2 adrenoceptor antagonists, 0.3-5 mg/kg yohimbine or 1 mg/kg atipamezole, 1 mg/kg of the alpha-1 antagonist prazosin, and 10-300 mg/kg of the nitric oxide synthase inhibitors, N omega-nitro-1-arginine methylester and N omega-nitro-1-arginine, were given 10-20 min before the agonist. The mice were killed by microwave radiation focused to the head. Cyclic GMP was measured by radioimmunoassay in deproteinized extracts from different brain areas. RESULTS: Clonidine and dexmedetomidine, at sedative doses, dose-dependently decreased cerebellar cGMP (ED50: 100 and 50 micrograms/kg for clonidine and dexmedetomidine, respectively). This effect was inhibited by yohimbine and atipamezole, but not by prazosin, confirming the alpha-2 nature of the response to the agonists. L-medetomidine, which has no sedative/hypnotic effect, did not decrease cGMP. Pretreatment of the mice with a maximum dose of 100 mg/kg of a nitric oxide synthase antagonist abolished the cGMP response to the agonists. Similar results were obtained in the cerebral cortex, hippocampus and caudate nucleus. CONCLUSIONS: The results suggest that the nitric oxide-cGMP pathway is an effector system coupled to the alpha-2 adrenoceptor mediating sedation.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1995

Lethal toxicity from equimolar infusions of cocaine and cocaine metabolites in conscious and anesthetized rats.

We compared the lethal toxicity of cocaine with that of three of its metabolites to determine the contribution of these metabolites to the lethal potential from cocaine infusion. Equimolar quantities of cocaine, norcocaine, benzoylecgonine, and ecgonine methyl ester were infused in conscious rats to determine onset of convulsions and respiratory arrest. In addition, the convulsive and respiratory toxicity for cocaine and norcocaine were evaluated in anesthetized rats and their circulatory toxicity in anesthetized and ventilated rats. Norcocaine infusion resulted in earlier onset of convulsions and respiratory arrest in conscious rats than cocaine and earlier onset of circulatory arrest. Plasma concentrations of norcocaine and cocaine were not different at these times. Benzoylecgonine and ecgonine methyl ester were less potent convulsants and respiratory depressants than norcocaine and cocaine, with ecgonine methyl ester more respiratory depressant than benzoylecgonine. Pentobarbital anesthesia enhanced the respiratory depression and suppressed or delayed the onset of convulsions from norcocaine and cocaine infusion. Prolonged infusion of cocaine to circulatory arrest resulted in benzoylecgonine concentrations approximately 60%, and norcocaine concentrations approximately 5%, of the cocaine concentration, but no detectable ecgonine methyl ester formation. We conclude that although norcocaine, ecgonine methyl ester, and benzoylecgonine administered separately have lethal potential in massive dosages, death from cocaine overdose primarily results from the parent compound and not from metabolite formation.

Animals↗

PubMed1994

Sensitive assay for cocaine and benzoylecgonine using solid-phase extraction and gas chromatography.

An improved method for the simultaneous determination of cocaine and benzoylecgonine by means of gas chromatography with nitrogen-phosphorus detection is described. Following a solid-phase extraction and derivatization of benzoylecgonine to its butyl ester, chromatography was performed using a capillary column. The n-propylester of benzoylecgonine served as the internal standard. The assay was linear from 4 to 2000 ng/ml for both cocaine and benzoylecgonine, with a good precision over this concentration range. This method may be particularly useful for small volume samples since it requires only 250 microliters of plasma for analysis of both cocaine and benzoylecgonine.

Chromatography, Gas↗