Harvey A. Schwertner

Suppression of ethanol withdrawal by dopamine.

An ethanol-inhalation technique was used to determine a potential relationship between dopamine and central nervous effects produced by alcohol. Bothl-DOPA and intracranially injected dopamine resulted in attenuation of ethanol-induced withdrawal convulsion scores, whereas, haloperidol, a known dopaminergic blocker was found to significantly increase convulsion scores.

POSSIBLE ROLE OF TETRAHYDROISOQUINOLINE ALKALOIDS IN POSTALCOHOL INTOXICATION STATES

Because norepinephrine (NE) and dopamine (DA) constitute the major catecholamines in the body, it IS possible that their tetrahydroisoquinoline (TIQ) derivatives (condensation products of biogenic amines and acetaldehyde), if formed in vivo after alcohol consumption, could contribute to some pharmacologic responses to ethanol by interfering with catecholaminergic (adrenergic and dopaminergic) mechanisms in the brain and in the periphery.’-3 The speculation that TIQ alkaloids may form in vivo during alcohol intoxication has been recently supported by the work of Collins and Bigdeli.4 These authors were able to identify TIQ in the brain of rats pretreated with L-Dopa, ethanol, ,and pyrogallol, a known catecholamine methyltransferase inhibitor.5 Sandler et a1.h also reported that administration of ethanol to Parkinson’s disease patients who were being treated with large doses of L-Dopa provoked urinary excretion of the TIQ condensation product of DA with acetaldehyde. Furthermore, the suggestion that TIQ alkaloids possess peripheral pharmacologic activity has now been documented in a report by Mytilineou e! al.7 These investigators showed that irides of mice or rats depleted of endogenous NE by treatment with a-methyl-p-tyrosine (a-M PT) again showed fluorescence after subsequent intravenous injections of 6,7-dihydroxytetrahydroisoquinoline (6,7-DTIQ). They also reported that during stimulated release of 6,7-DTIQ, there was marked retraction of the eyelid, protrusion of the eyeball, and dilation of the pupil. These responses were similar to those seen in normal (NE-containing) animals. The results suggested that the dopamine-derived TIQ possesses the properties of a false transmitter. The results of another study by Cohen et d7 also demonstrate CNS activity for 6,7-DTIQ due to its catecholamine-releasing properties. The results of a study from our laboratory that show that 6,7-DTIQ produced hyperexcitability, as measured by convulsions elicited by handling in mice, further demonstrate the central action of this TIQ alkaloid. The fact that the slopes of the first derivatives of dose-response curves are similar for N E and 6,7-DTIQ and are dissimilar for both

Thin-layer chromatographic analysis of cocaine and benzoylecgonine in urine

The sensitivity achieved by the described thin-layer chromatographic (TLC) method greatly exceeds that of previously published TLC methods for the determination of cocaine and its principal metabolite, benzoylecgonine, in urine. Sensitivity for cocaine and benzoylecgonine approaches 0.1 and 0.25 mug/ml, respectively, for a 5.0-ml specimen. A simple extraction with a mixed organic solvent provides the basic mechanism for isolating the drugs from biologic specimens. Cocaine and its metabolites are stable in sulfuric acid solutions but labile in aqueous media containing certain other inorganic and organic acids; therefore, an emphasis on the utilization of sulfuric acid solutions is employed throughout the procedure. An evaluation of sensitivities achieved for cocaine and benzoylecgonine by various detection reagents is presented. The technique is applicable to drug screening programs.

Identification of selected antihypertensive drugs by thin-layer chromatography.

A thin-layer chromatographic procedure is described for the qualitative identification of several antihypertensive drugs including certain thiazide diuretics spironolactone, triamterene, methyldopa and their metabolites. Utilization of new solvent developing systems and spray detecting reagents provides a method useful for the identification of these compounds in biologic fluids at low therapeutic concentrations. Sensitivity limits for these antihypertensive drugs are given, and alternate techniques to provide confirmatory analyses are also presented.

Intensification of amphetamine-induced excitation by methysergide, a serotonergic receptor blocker.

Methysergide, a serotonergic receptor blocker, was studied to determine its effects against d-amphetamine-induced excitation as measured by convulsions elicited by handling in mice. Significant intensification (p<0.01) of the action of d-amphetamine was observed in mice. These results indicate that reduction in serotonergic activity in the central nervous system enhances excitation induced by d-amphetamine.