Life sciences
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The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (LTPC) was used to form diastereomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) which were resolved on an achiral gas chromatographic column using a mass spectrometer as a detector. Rats were subcutaneously dosed with 40 mg/kg of (+/-) MDMA. HCl and blood was obtained by decapitation four hours after dosing. ⋯ In addition to the two MDMA isomers, the demethylated metabolites, S(+) and R(-)-MDA were identified. In all experimental groups (male rats, food deprived male rats, female rats, post partum female rats, and mice) dosed with racemic MDMA, higher levels of the S(+) isomer of MDA relative to the R(-) MDA isomer were observed. This may be significant since it has been shown that the S(+) isomer of MDMA is the more neurotoxic isomer of the racemic drug of abuse MDMA.
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Hypertonic (1M) sodium bicarbonate can partially reverse the cardiac toxicity of some Class IA antiarrhythmic agents, presumably by antagonizing sodium channel inhibition. We studied the effects of 1M sodium bicarbonate on toxicity due to the Class IC drug flecainide. Anesthetized rats received i.v. loading and maintenance doses of flecainide to produce QRS prolongation of 76% that was stable over the 60 min study period. 20 min after the start of the maintenance infusion, groups of 8 rats received an i.v. infusion of 1M sodium bicarbonate (6 meq/kg) or an equal volume of 0.9% saline. ⋯ Serum flecainide concentrations were similar. These data suggest that 1M sodium bicarbonate can partially reverse flecainide-induced conduction delay in rats. This effect may be due to changes in the extracellular pH and sodium concentration. 1M sodium bicarbonate may be useful in assessing the role of sodium channel inhibition in mediating the toxicity of flecainide or other Class IC drugs.