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Biomedical subjects

A Clow

Publications and source records attributed to A Clow.

At least 55 records · Page 3Linked to original sources
PubMed1991

Effect of aromatic amino acids, pentylenetetrazole and yohimbine on isatin and tribulin activity in rat brain.

The effects of i.p. injection of 3 aromatic amino acids and two anxiogenic agents on rat brain isatin concentration and tribulin (endogenous monoamine oxidase inhibitor) activity were investigated. Isatin levels were significantly increased by pentylenetetrazole, confirming the link with 'anxiety', but were unaffected by the other compounds. In contrast, tribulin activity was significantly increased by phenylalanine and tryptophan as well as by both pentylenetetrazole and yohimbine. Whilst these findings shed no light on the mode of synthesis of isatin, they clearly demonstrate the existence of rat brain monoamine oxidase inhibitory activity that is different from it.

Animals↗
PubMed1991

Isatin (indole-2,3-dione) in urine and tissues. Detection and determination by gas chromatography-mass spectrometry.

A simple procedure based upon capillary column gas chromatography-mass spectrometry (GC-MS) is described for the detection and determination of isatin (indole-2,3-dione) in body fluids and tissues. After addition of 5-methylisatin as internal standard to urine or tissue homogenates, organic extracts are dried and derivatized successively with hydroxylamine hydrochloride and the reagent N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA). The tert.-butyldimethylsilyl derivatives obtained show good GC-MS properties and allow quantification by selected-ion monitoring of m/z 333 (isatin) and m/z 347 (internal standard). Adult and newborn human urine output values lie in the ranges 0.4-3.2 mg/mmol of creatinine (5-30 mg per 24 h) and 0.002-0.518 mg/mmol of creatinine, respectively. There is a discontinuous regional distribution in rat tissues. The GC-MS properties of a number of derivatives formed by successive reaction of isatin with hydroxylamine hydrochloride (or methoxyaminehydrochloride or ethoxyamine hydrochloride) and MTBSTFA, bis(trimethylsiyl)trifluoroacetamide, pentafluoropropionic anhydride or pentafluorobenzyl bromide are also described.

Acetamides↗
PubMed1991

(-)-Deprenyl can induce soluble superoxide dismutase in rat striata.

(-)-Deprenyl (0.25 or 2 mg/kg) or saline was injected daily into male Wistar rats for 3 weeks. The striata were dissected out and soluble and particulate superoxide dismutase activity measured. (-)-Deprenyl at 2 mg/kg induced a significant increase in the soluble but not the particulate form of the enzyme. The possibility that this action contributes to the ability of (-)-deprenyl to retard nigral degeneration in man and prolong life in rats is discussed.

Animals↗
PubMed1989

Isatin and tribulin concentrations are increased in rabbit brain but not liver following pentylenetetrazole administration.

Isatin has recently been identified in rat tissues and normal human urine where it constitutes the major part of the endogenous monoamine oxidase inhibitor, tribulin. In this study, we have measured both isatin (by gas chromatography/mass spectrometry) and tribulin (inhibition of a standard rat liver monoamine oxidase preparation) in extracts of rabbit brains and livers after intravenous administration of the anxiogenic, proconvulsant agent pentylenetetrazole. There were increased levels of both isatin and tribulin in rabbit brains, but not in livers, after pentylenetetrazole, compared with saline treated controls. This finding supports the hypothesis that isatin is a component of tribulin activity and may have a role in anxiety or epilepsy.

Anxiety↗
PubMed1989

Stress reduces in vivo inhibition of monoamine oxidase by phenelzine in rat brain.

The level of inhibition of rat whole brain monoamine oxidase activity produced by the irreversible monoamine oxidase inhibitor phenelzine has been studied with or without concurrent cold restraint stress. We have found that phenelzine caused significantly less enzyme inhibition when given during a period of stress than during a control period. Thus, stress can reduce the in vivo potency of MAO inhibitors. This would be compatible with an increased production of the reversible, endogenous monoamine oxidase inhibitor, tribulin, competing for the active site of the enzyme.

Animals↗
PubMed1988

Increased urinary tribulin output in generalised anxiety disorder.

Urinary output of an endogenous monoamine oxidase inhibitor and benzodiazepine receptor binding inhibitor (tribulin) was raised in a group of patients with generalised anxiety disorder compared with controls. Tribulin levels remained relatively constant in individual patients over the 6-week period of observation, mean values remaining high even after reduction of anxiety following non-drug behaviour therapy.

Adult↗
PubMed1988

Tribulin in post-traumatic stress disorder.

Tribulin (endogenous monoamine oxidase inhibitor/benzodiazepine receptor binding inhibitor) output was measured in the urine of 18 patients with post-traumatic stress disorder (PTSD) and 13 controls. The level of the two inhibitory activities was highly significantly correlated in the group as a whole. There was no difference between output of either inhibitor in patients and controls. However, when the PTSD group was subdivided according to various psychometric ratings, a pattern of output did emerge. Levels of both inhibitory activities were higher in agitated compared with non-agitated subjects, and lower in extroverts compared with introverts. This finding supports the view that tribulin output is raised in conditions of greater arousal.

Arousal↗
PubMed1988

Isatin: identity with the purified endogenous monoamine oxidase inhibitor tribulin.

Purified tribulin, an endogenous monoamine oxidase (MAO) inhibitor, has been identified by direct probe insertion mass spectrometry as the indole-2,3-dione, isatin. A gas chromatographic-mass spectrometric assay for isatin has been developed and used to measure its relatively high concentrations in unpurified human urine, and in rat heart and brain. Isatin is a known compound with a broad range of biological activity; this is the first report of its presence in the animal body. Isatin is a potent inhibitor of MAO, particularly of MAO B (IC50, 3 microM), and also binds to central benzodiazepine receptors (IC50 against clonazepam, 123 microM).

Animals↗
PubMed1988

Urinary catecholamine metabolite and tribulin output during lactate infusion.

Urinary output of homovanillic acid and 4-hydroxy-3-methoxymandelic acid was decreased both in patients with panic attacks and in normal controls during lactate infusion, whereas that of tribulin (an endogenous monoamine oxidase inhibitor and benzodiazepine receptor binding inhibitor) was increased. There was no change in urinary excretion of any of these compounds during saline infusion. These findings provide further evidence of a link between tribulin output and stress and anxiety in man and point to its possible in vivo action as a monoamine oxidase inhibitor.

Anxiety Disorders↗
PubMed1986

Purification and characterization of tribulin, and endogenous inhibitor of monoamine oxidase and of benzodiazepine receptor binding.

A low molecular weight fraction of human urine (less than 500 daltons) which both inhibits monoamine oxidase and benzodiazepine binding to central and peripheral receptors has been purified by ethyl acetate extractions, HPLC and thin layer chromatography. This material extracted equally well at acid and basic pH and was insoluble in heptane. It competitively inhibited binding of 3H-clonazepam, a central benzodiazepine receptor agonist and, in addition, displaced 3H-Ro 5-4864, a specific peripheral benzodiazepine receptor ligand, from its binding sites. It showed no GABA shift with the benzodiazepine receptor antagonist, Ro-15 1788. MAO A and B were inhibited approximately equipotently and the material competitively inhibited tyramine oxidation by rat liver. It was stable on boiling and is unlikely to be a peptide.

Animals↗
PubMed1985

Effects of discontinuous drug administration on the development of dopamine receptor supersensitivity during chronic trifluoperazine or cis-flupenthixol administration to rats.

Rats received continuous or discontinuous administration of trifluoperazine or cis-flupenthixol in drinking water for up to 12 months. Continuous and discontinuous trifluoperazine administration had no consistent effect on apomorphine-induced stereotyped behaviour and there was no difference between drug treatments. Continuous and discontinuous cis-flupenthixol administration enhanced apomorphine-induced stereotypy, but there was no difference in the effect of the two drug treatments. Both continuous and discontinuous administration of trifluoperazine increased the number of specific striatal 3H-spiperone binding sites (Bmax). Over the period of treatment there was no difference in the effects of the different treatments. Continuous or discontinuous cis-flupenthixol intake did not increase Bmax after 6 or 12 months intake. Continuous or discontinuous neuroleptic treatment produced no difference in functional striatal dopamine receptor activity as judged by apomorphine-induced stereotyped behaviour. Ligand binding studies also suggest that the overall change in striatal receptor function is not affected by the use of a discontinuous drug regime.

Animals↗
PubMed1985

Triazolam, an anomalous benzodiazepine receptor ligand: in vitro characterization of alprazolam and triazolam binding.

Both alprazolam and triazolam displaced clonazepam (but not Ro 5-4864) from rat brain membranes with high affinity, showing them to act at central but not peripheral benzodiazepine receptors. At 0 degrees C, 10 microM gamma-aminobutyric acid (GABA) increased the ability of alprazolam, but not of triazolam, to displace ethyl-beta-carboline-3-carboxylate (beta-CCE) and Ro 15-1788 from these receptors. At 37 degrees C, GABA increased the affinity of the receptors for both drugs, with a +GABA/-GABA ratio of 1.5 for each in promoting Ro 15-1788 binding displacement. As both triazolam and alprazolam act as anxiolytics in vivo, the results at 37 degrees C would be compatible with the hypothesis that GABA causes an increase in affinity of drugs that act in this way, but the results at 0 degrees C would not be compatible. At 37 degrees C, alprazolam had a higher IC50 for the benzodiazepine receptor than at 0 degrees C, whereas triazolam showed the reverse effect. The relative IC50 values in vitro at 37 degrees C correlated better with the potency in vivo than those obtained at 0 degrees C. At 0 degrees C, both drugs showed Hill plots with slopes of 0.9-1 with beta-CCE and Ro 15-1788. At 37 degrees C, the slopes with triazolam were much reduced, indicating that the drug may have a selective action on a subclass of central benzodiazepine receptors. In the studies reported here, alprazolam behaved like other benzodiazepines, whereas triazolam showed several anomalous properties. It would be of interest if these properties could be related either to the drug's use as a hypnotic or to the side effects it sometimes induces.

Alprazolam↗
PubMed1985

Tribulin: an endogenous monoamine oxidase inhibitor/benzodiazepine receptor ligand.

Tribulin is a low molecular weight inhibitor both of monoamine oxidase and of benzodiazepine receptor binding. It has been highly purified from human urine and has also been isolated from human plasma and animal brain. Its structure is still unknown but its properties do not appear to correspond with any known monoamine or benzodiazepine receptor binding inhibitor. Tribulin output has been found to be increased in a variety of states associated with stress and anxiety, including lactate-induced panic attacks, alcohol or benzodiazepine withdrawal and generalized anxiety disorder.

Animals↗
PubMed1985

The role of salsolinol in alcohol intake and withdrawal.

We studied the urinary excretion of the tetrahydroisoquinoline (TIQ) salsolinol, formed from acetaldehyde and dopamine, in both severely and moderately dependent alcoholics during withdrawal from alcohol and subsequent challenge with an acute dose of alcohol and L-dopa, and compared these results with controls. Plasma acetaldehyde and alcohol levels in a sub-population of severely dependent withdrawn alcoholic and control subjects following an acute dose of alcohol were also determined. Salsolinol excretion during the first 4 days of alcohol withdrawal was variable but 10 out of 14 alcoholics showed an increasing trend from day 1 to day 3 and 4 of alcohol withdrawal. L-dopa administration raised salsolinol excretion in controls and withdrawn alcoholics to a uniform extent. Loading of the withdrawn alcoholics with an acute dose of alcohol did not cause an increase in urinary salsolinol concentration (despite increased plasma acetaldehyde). Indeed, 24 h following acute alcohol administration, salsolinol excretion rates were depressed in the alcoholics but not in the controls.

Acetaldehyde↗
PubMed1983

New endogenous benzodiazepine receptor ligand in human urine: identity with endogenous monoamine oxidase inhibitor?

Normal human urine contains both monoamine oxidase-inhibiting and benzodiazepine receptor-binding material. Each was extracted into ethyl acetate at pH 1 and subjected to high performance liquid chromatography: they ran similarly, showing three major peaks. The correlation coefficient between the pattern of MAO inhibition and inhibition of 3H-flunitrazepam binding to benzodiazepine receptors in the second half of the elution process was 0.78 (p less than 0.001): most UV-absorbing material present was eluted earlier in the run. These results are compatible with, although they do not prove, the hypothesis that the endogenous MAO inhibitor, previously shown to be increased in stress, is also an endogenous inhibitor of 3H-flunitrazepam binding to the benzodiazepine receptor. This material is different from other putative endogenous ligands: it migrates more rapidly than the potent but artefactual beta-carboline-3-carboxylic acid ethyl ester previously isolated from human urine; nor can the effect we have identified derive from harmane, inosine, hypoxanthine or nicotinamide which fail to extract into ethyl acetate at pH 1.

Adult↗