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Biomedical subjects

B A Davis

Publications and source records attributed to B A Davis.

At least 73 records · Page 4Linked to original sources
PubMed1993

The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog.

Behavioral and pharmacological effects of oral administration of L-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected by L-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested that L-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects of L-deprenyl on behavior and cognitive function.

Administration, Oral↗
PubMed1993

Effects of chronic brofaromine administration on biogenic amines including sulphatoxymelatonin and acid metabolites in patients with bulimia nervosa.

Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), beta phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.

Adolescent↗
PubMed1993

A longitudinal study of the relationships between psychometric test scores, offence history and the plasma concentrations of phenylacetic and 5-hydroxyindoleacetic acids in seven inmates of a prison for the psychiatrically disturbed.

1. The plasma concentrations of phenylacetic (PAA) and 5-hydroxyindoleacetic (5HIAA) acids in seven inmates incarcerated in the Regional Psychiatric Centre (Prairies), Correctional Service of Canada, were assessed each weekday for four weeks (i.e., 20 samples each). Psychometric assessments for hostility, anger, depression and anxiety were also performed daily. Mean differences between subjects in psychometric and biochemical measures were subjected to tests of statistical significance. 2. The subject who was clearly most aggressive by offence history/institutional behavior scored significantly highest on scales of anger and hostility and significantly lowest with respect to PAA concentration. It was concluded that PAA may be a trait marker for aggression. 3. Plasma 5HIAA concentrations were invariant between subjects. 4. The psychometric measures were intercorrelated, thus confounding the variables of interest. They also varied little, proving insensitive to subtle mood changes.

Adult↗
PubMed1993

The effect of the MAO-A selective inhibitor brofaromine on the plasma and urine concentrations of some biogenic amines and their acidic metabolites in bulimia nervosa.

1. Brofaromine or placebo were administered to female bulimia nervosa patients over a period of eight weeks. Plasma and urinary trace amines, their acidic metabolites and the acidic metabolites of the catecholamines and serotonin were assessed prior to treatment and at four and eight weeks after commencement of treatment. 2. The levels of both plasma and urinary homovanillic and vanilmandelic acids declined significantly during the first four weeks of treatment with brofaromine and then partially recovered to pre-drug levels by the eighth week. 5-Hydroxyindoleacetic acid levels were not affected by drug treatment at the times assessments were made. Urinary tryptamine increased significantly during the first four weeks of brofaromine treatment then partially recovered towards pre-drug levels by the eighth week. No effect from placebo treatment was observed.

Biogenic Amines↗
PubMed1992

Aliphatic propargylamines: potent, selective, irreversible monoamine oxidase B inhibitors.

A series of aliphatic propargylamine derivatives has been synthesized. Some of them possess highly potent, irreversible, selective, inhibitory activity toward monoamine oxidase B (MAO-B). The potency of the inhibitors is related to chain length and substitution of a hydrogen on the terminal carbon of the aliphatic chain. MAO inhibitory activity as assessed in vitro increased as the aliphatic carbon chain length increased. Substitution of a hydrogen by hydroxyl, carboxyl, or carbethoxyl groups at the aliphatic chain terminal or replacement of the methyl group on the nitrogen atom by an ethyl group considerably reduced the inhibitory activity. Stereospecific effects were observed with the R-(-)-enantiomer being 20-fold more active than the S-(+)-enantiomer. Inhibitors with relatively short carbon chain lengths (i.e. four to six carbons) were found to be more potent than those with longer chains in inhibiting brain MAO-B activity in vivo especially after oral administration. Chronic administration of low doses of the aliphatic propargylamines caused a slight cumulative inhibition of MAO-A activity in the mouse brain. These MAO-B inhibitors appear to be nontoxic, and they do not possess an amphetamine-like moiety in their structure as is the case for deprenyl. We expect that these aliphatic propargylamines may be useful in the treatment in certain neuropsychiatric disorders.

Animals↗
PubMed1992

Role of G proteins in stimulation of Na-H exchange by cell shrinkage.

Many cells respond to shrinkage by stimulating specific ion transport processes (e.g., Na-H exchange). However, it is not known how the cell senses this volume change, nor how this signal is transduced to an ion transporter. We have studied the activation of Na-H exchange in internally dialyzed barnacle muscle fibers, measuring intracellular pH (pHi) with glass microelectrodes. When cells are dialyzed to a pHi of approximately 7.2, Na-H exchange is active only in shrunken cells. We found that the shrinkage-induced stimulation of Na-H exchange, elicited by increasing medium osmolality from 975 to 1,600 mosmol/kgH2O, is inhibited approximately 72% by including in the dialysis fluid 1 mM guanosine 5'-O-(2-thiodiphosphate). The latter is an antagonist of G protein activation. Even in unshrunken cells, Na-H exchange is activated by dialyzing the cell with 1 mM guanosine 5'-O-(3-thiotriphosphate), which causes the prolonged activation of G proteins. Activation of Na-H exchange is also elicited in unshrunken cells by injecting cholera toxin, which activates certain G proteins. Neither exposing cells to 100 nM phorbol 12-myristate 13-acetate nor dialyzing them with a solution containing 20 microM adenosine 3',5'-cyclic monophosphate (cAMP) (or 50 microM dibutyryl cAMP) plus 0.5 mM 3-isobutyl-1-methylxanthine substantially stimulates the exchanger. Thus our data suggest that a G protein plays a key role in the transduction of the shrinkage signal to the Na-H exchanger via a pathway that involves neither protein kinase C nor cAMP.

Animals↗
PubMed1992

Activation of Na-H exchange by intracellular lithium in barnacle muscle fibers.

We internally dialyzed single barnacle muscle fibers (BMF) for 90 min with a dialysis fluid (DF) containing no Na+ and either 0 or 100 mM Li+ and measured intracellular pH (pHi) with a microelectrode. During dialysis, the pH 8.0 artificial seawater (ASW) contained neither Na+ nor HCO3-. After we halted dialysis with a Li(+)-free/low-pH DF and allowed pHi to stabilize at approximately 6.8, adding 440 mM Na(+)-10 mM HCO3- to the ASW caused pHi to recover rapidly and stabilize at 7.32. In contrast, when the DF contained 100 mM Li+, pHi stabilized at 7.49. In fibers dialyzed to a pHi of approximately 7.2, Li+ stimulated a component of acid extrusion that was dependent on Na+ but not affected by SITS. Thus Li+ activates a Na(+)-dependent acid-extrusion mechanism other than the well characterized Na(+)-dependent Cl-HCO3 exchanger. To study the Li(+)-activated mechanism, we minimized Na(+)-dependent Cl-HCO3 exchange by raising pHDF to 7.35 and pretreated BMFs with SITS. We found that dialysis with Li+ elicits a Na(+)-dependent pHi increase that is largely blocked by amiloride, consistent with the hypothesis that Li+ activates a latent Na-H exchanger even at a normal pHi. In the absence of Li+, the Na-H exchanger is relatively inactive at pHi 7.35 (net acid-extrusion rate, Jnet = 9.5 microM/min) but modestly stimulated by reducing pHi to 6.8 (Jnet = 64 microM/min). In the presence of Li+, the Na-H exchanger is very active at pHi values of both 7.35 (Jnet = 141 microM/min) and 6.8 (Jnet = 168 microM/min). Thus Li+ alters the pHi sensitivity of the Na-H exchanger. Because the Na-H exchanger is only approximately 6% as active as the Na(+)-dependent Cl-HCO3 exchanger in the absence of Li+ at a pHi of approximately 6.8, we suggest that the major role of the Na-H exchanger may not be in pHi regulation but in another function such as cell-volume regulation.

Acids↗
PubMed1991

Longitudinal effect of amitriptyline and fluoxetine treatment on plasma phenylacetic acid concentrations in depression.

Unconjugated (U-PAA), conjugated (C-PAA), and total phenylacetic acid (T-PAA) concentrations in blood plasma and monoamine oxidase (MAO) activity in platelets towards phenylethylamine (PE) were determined in 40 drug-free, depressed patients (23 melancholic, 17 nonmelancholic) from five psychiatric treatment centers, and in 34 normal healthy volunteers. No significant differences were found between controls and all depressed patients or between melancholic and nonmelancholic depressed patients. Treatment of the depressed patients with amitriptyline or fluoxetine over a 6-week period resulted in clinical improvement and in a significant increase in plasma PAA concentrations. A decline in the Beck and Hamilton rating scores during treatment correlated significantly with increases in the concentrations of unconjugated, conjugated, and total phenylacetic acid but not with MAO activity, which did not change during treatment. At each of the three assessment times, however, plasma PAA concentrations and psychiatric rating scores were not significantly correlated. Except for higher end-of-study T-PAA concentrations in the amitriptyline-treated subjects, no significant differences were found between the effects of the two drugs with regard to plasma phenylacetic acid levels, MAO activity, or rating scores.

Adult↗
PubMed1991

Plasma phenylethylamine in schizophrenic patients.

Plasma samples were collected from 41 patients who met DSM-III criteria for schizophrenia and from 34 healthy controls. Phenylethylamine (PE) levels were determined using a gas chromatography-mass spectrometry negative chemical ionization method. PE was significantly higher in the schizophrenic patients compared with controls. There were no differences in PE between paranoid and nonparanoid patients. Plasma PE did not appear to be influenced by the severity of schizophrenic symptoms (rated by BPRS, SANS, and SAPS) or by the amount of dietary phenylalanine ingested within 24 hr of testing. Plasma PE did not correlate with current or past exposure to neuroleptic medication. It was not possible, however, to test individual patients during two periods when they were taking and not taking medication. Thus it is possible that neuroleptic exposure may have confounded the results. This study provides further evidence that PE excess may play a role in the etiology of schizophrenia but does not support previous studies which suggest that such an abnormality is limited to the paranoid subgroup.

Adult↗
PubMed1991

Quantification of plasma phenylethylamine by combined gas chromatography/electron capture negative ion mass spectrometry of the N-acetyl-N-pentafluorobenzoyl derivative.

An ultrasensitive method capable of detection and quantification of beta-phenylethylamine in 1 ml of human plasma has been developed using gas chromatography/electron capture negative ion mass spectrometry. Phenylethylamine and tetra-deutero phenylethylamine internal standard in plasma were acetylated, extracted into organic solvent and then further acylated with pentafluorobenzoyl chloride. The N-acetyl-N-pentafluorobenzoyl-phenylethylamines were detected by high-resolution single ion monitoring of the molecular ions. Normal plasma levels were found to be 41.5 +/- 10.7 pg ml-1, in accordance with results of a previous high-performance liquid chromatographic method.

Chromatography, Gas↗
PubMed1991

Simultaneous delivery of valproic acid and glycine to the brain. Deamination of 2-propylpentylglycinamide by monoamine oxidase B.

2-Propylpentylglycinamide (2-PPG), a branched aliphatic amine derivative, was found to be readily deaminated by rat liver monoamine oxidase B in vitro and in vivo. The deamination leads to production of 2-propyl-1-pentaldehyde, which can be subsequently converted to valproic acid (VPA), and glycinamide, which is then subsequently converted to glycine. Absorption and biotransformation of a single ip dose of 2-PPG into blood as well as transfer of the drug and its metabolite into the brain were rapid processes. Although VPA (an anticonvulsant) and glycine (an inhibitory neurotransmitter) can be detected in the brain following administration of 2-PPG, its anticonvulsant action cannot be determined. 2-PPG at relatively low doses exhibited distinct tremor effects. Furthermore, 2-PPG appeared to potentiate the convulsant effect induced by pentylenetetrazol.

Animals↗
PubMed1991

2-propyl-1-aminopentane, its deamination by monoamine oxidase and semicarbazide-sensitive amine oxidase, conversion to valproic acid and behavioral effects.

2-Propyl-1-aminopentane (2-PAPN), a branched aliphatic amine, was found to be readily deaminated by monoamine oxidase B in the liver of the rat and semicarbazide-sensitive amine oxidase in the aorta of the rat. The deaminated product, 2-propyl-1-pentaldehyde, could be subsequently converted to valproic acid in the presence of aldehyde dehydrogenase and beta-NAD cofactor in vitro as well as in vivo. Valproic acid was identified after derivatization with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC-fluorometric assessment. Absorption and biotransformation of a single intraperitoneal dose of 2-PAPN resulted in the rapid appearance of the drug and its metabolite in the blood and in the brain. The formation of valproic acid from 2-PAPN in vivo, however, was insufficient to facilitate anticonvulsant action. In fact, 2-PAPN itself, at relatively small doses, exhibited distinct tremor effects. Such tremor effects could be prevented by valproic acid. However, 2-PAPN was also found to potentiate the convulsant effect induced by mercaptopropionic acid (MPA) and, in addition, the 2-PAPN-induced tremor could be potentiated by MPA in mice.

Amines↗
PubMed1991

Longitudinal study of inmates of a prison for the psychiatrically disturbed: plasma concentrations of biogenic amine metabolites and amino acids.

Plasma concentrations of eight large and neutral amino acids and 10 acidic metabolites of biogenic amines in seven inmates incarcerated in the Regional Psychiatric Centre (Praries), Correctional Service of Canada, were assessed each week day for 4 weeks (i.e., 20 samples each). Measures of central tendency and dispersion of the variables were calculated. The measures are distinctively different in their variability and their normality of distribution. The large and neutral amino acid (LNAA) measures are somewhat less variable, but also less likely to be normally distributed than most acid metabolites. Acid metabolites tend to show consistent interindividual differences that persist over time, with the notable exception of 5-hydroxyindoleacetic acid. LNAA measures tend to show differences across time but not between individuals. The distributional properties of LNAA measures are largely accounted for by the observation of a downward convergence of values of these variables over the 4 weeks of the study.

Adult↗
PubMed1991

The effect of age, sex, weight and height on the plasma concentrations in healthy subjects of the acidic metabolites of some biogenic monoamines involved in psychiatric and neurological disorders.

1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply for both males and females but are significant only for males. 3. Homovanillic and vanillylmandelic acid concentrations in plasma increase with age. 4. The importance of using age, sex, weight and height matched groups in studies involving the plasma concentrations of some of the trace amine metabolites in psychiatric disorders has been demonstrated. This is particularly the case for phenylacetic acid, the major metabolite of phenylethylamine which is now thought to be a neuromodulator of catecholaminergic neurotransmission.

Adult↗
PubMed1991

Phenylacetic acid in CSF and serum in Indian schizophrenic patients.

1. It has been proposed that an increase in the concentration of the neuromodulator phenylethylamine at the post-synaptic dopamine receptor may be involved in the etiology of schizophrenia. If this increase is the case, a reduction in the CSF and/or serum concentrations of phenylacetic acid, its major metabolite, might be anticipated. 2. The authors have found in hospitalized Indian schizophrenic patients ingesting antipsychotic drugs, that the paranoid subgroup did indeed exhibit lower levels of unconjugated, conjugated and total phenylacetic acid in both serum and CSF.

Adult↗
PubMed1991

Effect of dietary phenylalanine on the plasma concentrations of phenylalanine, phenylethylamine and phenylacetic acid in healthy volunteers.

1. Phenylethylamine has been proposed as a neuromodulator in several psychiatric and other brain disorders, and its concentration and that of its major metabolite, phenylacetic acid, in plasma may prove useful as state or trait markers in diagnosis, treatment or in the elucidation of biochemical mechanisms of these disorders. 2. The effect of dietary phenylalanine intake and changes in dietary phenylalanine intake on the plasma concentrations and changes in plasma concentrations, respectively, of phenylalanine, phenylethylamine and unconjugated and conjugated phenylacetic acid have been investigated. 3. Dietary phenylalanine affects the concentration of plasma phenylalanine on the following day, but has no effect on phenylethylamine or phenylacetic acid concentrations. Thus single measurements per subject of phenylethylamine or phenylacetic acid do not need to take dietary factors into account. 4. Changes in dietary phenylalanine (whether in absolute amount or in the proportion of phenylalanine in the diet) are significantly correlated with changes in unconjugated phenylacetic acid. Therefore, in longitudinal studies, dietary factors should be taken into account.

Adult↗
PubMed1991

Deuterium-labelled p-tyramine challenge test and phenolsulfotransferase activity in depressed patients--failure to replicate decreased p-tyramine conjugation in depression.

1. Depressed and normal subjects were challenged with deuterium-labelled p-tyramine and urine was collected for 3 h. 2. Urinary excretion of conjugated p-tyramine was not significantly different between normal, melancholic and non-melancholic depressed subjects. 3. Platelet phenolsulfotransferase activity to p-tyramine (p less than 0.05) and to phenol (p less than 0.005) were significantly lower in the depressed patients.

Amitriptyline↗