Haroutune Dekirmenjian

An improved procedure of 3-methoxy-4-hydroxyphenyl-ethylene glycol determination by gas-liquid chromatography

Abstract A method for the quantitative determination of MHPG from urine by gas-liquid chromatography is described. Conditions for the hydrolysis of conjugated MHPG and isolation of free MHPG by organic extraction is discussed. High recovery, reproducibility, and specificity are obtainable with this method. The mean 24 hour MHPG urinary excretion for 5 males was 1600 ± 380 μg and for 6 females 1320 ± 360 μg.

Urinary catecholamine metabolites during behavioral changes in a patient with manic-depressive cycles.

3-Methoxy-4-hydroxyphenylglycol and normetanephrine were analyzed in daily urine specimens of a patient with manic-depressive cycles who was studied longitudinally. The quantities of these catecholamine metabolites excreted into urine were decreased during periods of depression as compared with periods of mania. Urinary excretion of 3-methoxy-4-hydroxyphenylglycol varied cyclically with a period length of approximately 20 days. Changes in this metabolite, and perhaps in normetanephrine, preceded the affective and behavioral shifts.

Excretion of catecholamine metabolites following intraventricular injection of 6-hydroxydopamine in the Macaca speciosa☆

Abstract Seven non-human primates ( Macaca speciosa ) were stereotaxically implanted with Kopf cannulae with the tip being placed at the junction of the lateral and third ventricles. Following a recovery period, 2 24-hr baseline urine specimens were collected from each animal. 4 of the animals were given intraventricular (i. vent.) injections of 1, 2, 4 and 8 mg of 6-hydroxy-dopamineṡHBr (6-OH-DAṡHBr) at 12-hr intervals ( in 1 ml of artifical CSF) and 7 days later a final injection of 16 mg of 6-OH-DAṡHBr. 3 control animals were given artificial CSF + equimolar NaBr injections on a similar schedule. Following the i. vent. injections 24-hr urine specimens were collected at periodic intervals. Urines were assayed for normetanephrine (NM), metanephrine (M), 3-methoxy-4-hydroxy-mandelic acid (VMA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). All animals were sacrificed 16 days after the final i. vent. injections and 14 areas of brain, adrenal gland, heart, and thoracic sympathetic chain were removed and assayed for norepinephrine (NE). It has been found that it is possible with this schedule of injection of 6-OH-DA to produce animals which have significantly reduced levels of brain NE (70% depletion) without decreasing NE in tissues outside the CNS. Such experimental animal preparations should be of particular use in studies in which a separation of peripheral from central noradrenergic systems is desirable. No differences in the excretion of NM, M, VMA, and MHPG between baseline and post-injection periods were found in those animals which were injected with artificial CSF only. In all animals which were given intraventricular 6-OH-DA and in which there was a decrement in brain NE without a depletion of NE in tissues outside the central nervous system, there was a significant decrement in urinary MHPG between the baseline and post-injection periods while no differences in the excretion of NM, M, or VMA were found. Based upon these data calculations were made which suggest that a significant fraction of urinary MHPG has its origin in metabolism of NE in brain.

NEUROENDOCRINE AND AMINE STUDIES IN AFFECTIVE ILLNESS

SUMMARY (1) There are limitations to some of these studies because of the small number of patients involved, but our data suggest that maximal Growth Hormone (GH) levels after induced hypoglycemia were lower in depressed patients than in control subjects. (2) Manic patients showed low GH peaks during the Insulin Tolerance Test (ITT), and furthermore urinary 3-methoxy-4-hydroxyphenylene glycol (MHPG) excretion rates in mania were indistinguishable from normals but higher than in depressed patients. (3) The apomorphine-induced GH response was essentially normal in affective disorder patients, while acute schizophrenic patients showed hypersensitivity of postsynaptic dopamine receptors. (4) Confirming previous studies by Maas et aL (1968, 1972), patients with depressive illness were found to have siguicantly lower urinary MHPG excretion, whereas borderline patients with depressive symptomatology had MHPG values similar to control subjects.

Dystonic reactions following neuroleptics: Time Course and proposed mechanisms

The occurrence of acute dystonic reactions was studied relative to drug pharmacokinetic parameters following a single dose of the phenothiazine, butaperazine. Dystonias occurred more than one half-life from peak butaperazine levels, 23 to 56 h after drug administration. The authors postulate that the appearance of dystonias on falling plasma concentrations may be due to disruption of dopaminergiccholinergic balance caused by differential antidopaminergic and anticholinergic potencies of the drug.

Norepinephrine metabolism and clinical response to dextroamphetamine in hyperactive boys.

The 24-hour urinary catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol, normetanephrine, and metanephrine were measured in 23 hyperactive boys and 13 matched healthy controls. The hyperactive children excreted lower MHPG and higher NM (low MHPG/NM ratio) amounts than in controls. The administration of d-amphetamine in the dose of 0.5 mg/kg body weight divided over two doses daily for two weeks decreased MHPG excretion in the hyperactive children. When the hyperactive children group was divided into drug responders and nonresponders according to their pre- and post-treatment scores on the Conners Teacher Questionnaire, d-amphetamine administration decreased MHPG excretion in the responders and did not change it in the nonresponders. Percent decrease in MHPG excretion correlated significantly with percent change in the hyperactivity factor of the questionnaire on the Spearman Rank Order Correlation Coefficient. Pretreatment urinary metabolites did not differentiate the responders from nonresponders. It is suggested that a relationship between CNS norepinephrine metabolism and hyperactivity exists and that d-amphetamine may achieve its therapeutic action in hyperactive children by altering CNS NE metabolism.

Blood Levels of Haloperidol in Schizophrenic Patients

Plasma and red blood cell levels of haloperidol were measured in psychotic patients after an acute dose of haloperiodol and during treatment with fixed doses for several weeks. There was wide variability of haloperidol plasma and red blood cell levels at a given dose and a nonlinear relationship between haloperidol dose and blood levels. The red blood cell/plasma ratio (0.40) had a narrow range among different patients. Haloperidol blood levels were not correlated with the age of the patient. Concomitant administration of benztropine mesylate did not decrease plasma haloperidol levels. Steady state plasma or red cell haloperidol levels could not be predicted from levels 24 hours after the acute dose.

Determination of cocaine in human urine, plasma and red blood cells by gas-liquid chromatography.

This paper describes a sensitive and reliable method for the determination of cocaine in human urine, plasma and red blood cells. Cocaine is extracted into cyclohexane from the biological materials at slightly alkaline pH, reduced with lithium aluminium hydride, acylated with pentafluoropropionic anhydride and detected by an electron capture detector. When compared with a gas chromatography-mass spectrometry method the results of cocaine determination correlated highly (r = 0.986). When cocaine was given intravenously to volunteer subjects only 0.2-1.4% of the administered dose was excreted as unmetabolized cocaine in the first 9 h after administration. Plasma and red blood cell levels of cocaine were also determined by this method after intravenous administration.

Quantitative determination of cocaine and its metabolites benzoylecgonine and ecgonine by gas—liquid chromatography

A sensitive and reliable method was developed to determine quantitatively cocaine and its metabolites benzoylecgonine and ecgonine. The method involved the formation of fluoro derivatives which were separated on 3% and 5% OV-1 columns and detected in picomole quantities using an electron capture detector. Ecgonine and benzoylecgonine were derivatized with a mixture of hexafluoroisopropanol-heptafluorobutyric anhydride (1:2). Cocaine was first reduced by LiAlH4 and then acylated by pentafluoropropionic anhydride. Benzoylecgonine, but not ecgonine, could also be determined by reduction and subsequent acylation. This provided the basis for the determination of cocaine, benzoylecgonine and ecgonine from the same sample. Cocaine could be determined in urine and plasma by this method.

The identification of depressed patients who have a disorder of ne metabolism and/or disposition

Abstract The data given here lead us to conclude that in a subgroup of depressed patients who may be identified clinically (primary affective disorders), biochemically (low MHPG), and pharmacologically (good response to desipramine, imipramine and amphetamine), there is a significant alteration in the metabolism and/or disposition of NE which is integral to the depressive illness per se .