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A E Halaris

Publications and source records attributed to A E Halaris.

At least 19 recordsLinked to original sources
PubMed1993

Characterization of subtypes of alpha-2 adrenoceptors in the human brain.

Radioligand binding studies have demonstrated that oxymetazoline has a high affinity for alpha-2A receptors, but lower affinities for alpha-2B and alpha-2C receptors. In contrast, prazosin has high affinity for alpha-2B and alpha-2C receptors, but relatively lower affinity for alpha-2A receptors. We exploited the respective selectivity of oxymetazoline and prazosin for alpha-2A and alpha-2B/2C adrenoceptors, respectively, to describe pharmacologically and to locate neuroanatomically alpha-2 adrenoceptor subtypes in the human brain. Competition curves for the inhibition of [3H]yohimbine binding by oxymetazoline and prazosin in homogenates of human caudate nucleus were fit best by a model assuming binding to two sites (P < .005). A concentration (CONCopt) of oxymetazoline and prazosin was calculated from these curves that would optimally antagonize binding of [3H]yohimbine to high-affinity sites, minimally inhibiting low-affinity binding. In the presence of CONCopt of prazosin, competition studies of remaining [3H]yohimbine binding in cerebral cortex revealed a rank order potency and potency ratios of compounds which were characteristic of alpha-2A receptors. In the presence of CONCopt of oxymetazoline, competition studies of remaining [3H]yohimbine binding in caudate revealed a rank order potency and potency ratios of compounds which were characteristic of alpha-2C receptors. The existence of a small population of alpha-2B adrenoceptors in the caudate could not be ruled out because slopes of competition curves of compounds which distinguish alpha-2B and alpha-2C adrenoceptors were shallow at oxymetazoline-insensitive sites. The percentages of [3H]yohimbine binding that were inhibited by the CONCopt of oxymetazoline and prazosin were determined in numerous brain regions. Oxymetazoline-sensitive binding of [3H]yohimbine predominated in most regions except for the caudate nucleus, where prazosin-sensitive binding was greatest.

Binding Sites↗
PubMed1992

Reduced neuropeptide Y concentrations in suicide brain.

Neuropeptide Y (NPY) was measured in postmortem brain tissue from victims of suicide and from individuals dying a sudden natural or accidental death (controls). Concentrations of NPY-immunoreactivity were measured by radioimmunoassay in frontal cortex (BA 10), temporal cortex (BA 22), caudate nucleus, and cerebellum. Concentrations of NPY-immunoreactivity were significantly lower in postmortem frontal cortex (-14%) and caudate nucleus (-27%) from suicide victims compared with age-matched controls. A subgroup of suicides with evidence of a history of depression revealed more robust reductions in concentrations of NPY-immunoreactivity in frontal cortex and caudate nucleus, as did four individuals who died from natural causes and also were described as having a possible history of depression. Concentrations of NPY-immunoreactivity in temporal cortex and cerebellum from victims of suicide or from the subgroup of subjects with a possible history of depression were not significantly different from those of age-matched controls. We suggest there is a deficit in the brain NPY system leading to region-specific reductions in peptide concentrations in subjects who have a history of depression.

Adolescent↗
PubMed1991

Chronic desipramine treatment reduces regional neuropeptide Y binding to Y2-type receptors in rat brain.

Chronic treatment of rats with desipramine and imipramine (5 mg/kg/twice daily/i.p.) for 14 days caused a significant reduction in the binding of [3H]propionyl NPY to membranes prepared from frontal cortex, nucleus accumbens, hypothalamus and hippocampus. There was no change in binding of [3H]propionyl NPY in the parieto-occipital cortex, striatum or amygdala. Scatchard analysis of binding data from frontal cortical and hippocampal membranes showed that [3H]propionyl NPY bound to a single site with a Kd of approximately 0.3 nM. The loss of [3H]propionyl NPY binding in hippocampal and frontal cortical membranes revealed that chronic tricyclic antidepressant treatment produced a reduction in the number of binding sites with no change in the affinity for the ligand. Chronic desipramine treatment did not alter the ability of NPY (0.01-25 microM) to stimulate inositol phosphate accumulation in rat frontal cortical slices as compared to saline-treated animals. The lack of change of NPY-induced inositol phosphate accumulation following chronic desipramine treatment showed that there was no change to Y1 NPY-type receptors which are linked to the hydrolysis of inositol phospholipids. However, the ability of NPY (0.05-0.5 microM) to inhibit forskolin (1 microM) stimulated adenylate cyclase via Y2 NPY-type receptors in rat frontal cortical slices was significantly reduced following chronic desipramine treatment. This finding suggests that the reduction of [3H]proprionyl NPY binding in selective brain regions may be the result of an antidepressant-induced loss of Y2-type NPY receptors which are negatively linked to adenylate cyclase.

Animals↗
PubMed1991

CSF and endocrine studies of premenstrual syndrome.

Eight women with prospectively documented premenstrual syndrome (PMS) underwent multiple samplings for estradiol, progesterone, prolactin, cortisol, and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) during an asymptomatic midcycle (late follicular) and a symptomatic premenstrual (late luteal) phase of the menstrual cycle. Cerebrospinal fluid (CSF) was collected for analysis of MHPG, norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), gamma-aminobutyric acid (GABA), homovanillic acid (HVA), tyrosine, tryptophan, beta-endorphin, prostaglandins, adrenocorticotropic hormone (ACTH), and arginine vasopressin (AVP). In subsequent months, a dexamethasone suppression test (DST) and a thyrotropin-releasing hormone (TRH) stimulation test were performed during midcycle and premenstrual phases. Significant results included increased CSF concentrations of MHPG in the premenstrual, as compared with the midcycle, phase of the cycle, and increased plasma cortisol concentrations during the midcycle phase. The DST showed a 62% overall rate of nonsuppression, irrespective of menstrual cycle phase. Though there were no abnormalities of thyrotropin-stimulating hormone (TSH) after TRH stimulation, the mean delta maximum prolactin values after TRH stimulation were higher than reported normal values both at midcycle and premenstrually. These pilot data suggest hormonal axes that might be worthy of further systematic investigation in future studies of PMS.

Adult↗
PubMed1990

A comparison of the binding of [3H]proprionyl-neuropeptide Y to rat and human frontal cortical membranes.

The binding characteristics of [3H]proprionyl-neuropeptide Y ([3H]proprionyl-NPY) were studied in frontal cortical membranes prepared from rat and human postmortem tissue. The specific binding of NPY decreased as the magnesium concentration increased from 1.05 to 10 mM. The binding was also influenced by the concentration of GTP in the buffer medium, with a resulting 45% decrease in NPY binding in the presence of 10(-6) M GTP. Using equilibrium binding studies, [3H]proprionyl-NPY was found to bind in both tissues with high affinity to a single class of receptors with a similar KD (0.035 nM). However, kinetic experiments in both tissues provided evidence for two components of [3H]proprionyl-NPY binding which may be related to receptor states. Competition binding experiments showed that peptide YY (PYY) was equal to NPY in its ability to displace [3H]proprionyl-NPY, whereas rat and human pancreatic polypeptide were without effect up to a concentration of 10(-6) M. This suggests that, whereas PYY and NPY may compete for the same receptor(s), the pancreatic polypeptides probably act on a separate population of receptors.

Animals↗
PubMed1989

Apparent phase advance in diurnal MHPG rhythm in depression.

Several investigators have proposed that diurnal rhythms, particularly that of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), show abnormalities in affective disorders. The present study compared diurnal MHPG rhythms in the plasma of 18 male depressed patients and 12 healthy male volunteers. A diurnal rhythm of MHPG closely fit to a cosine model was observed in volunteers and, to a lesser extent, in depressed patients. Patients, especially those with endogenous depression (N = 11), demonstrated an earlier acrophase (mean +/- SD = 12.53 +/- 3.38 hours), and treatment with desipramine was associated with a significant (3-hour) phase delay. This study confirms and extends previous reports of apparent phase advances in circadian noradrenergic rhythms in depressed patients.

Adult↗
PubMed1985

Diurnal rhythm of 3-methoxy-4-hydroxyphenylglycol (MHPG): relationship between plasma and urinary levels.

Plasma and urinary levels of MHPG were determined in six normal volunteers. Samples were obtained at 3-hour intervals for plasma and at 12-hour intervals for urine. Acrophase, amplitude and period were determined for plasma MHPG levels. A sinusoidal pattern was obtained for diurnal plasma MHPG with a peak at 15:00 hrs. +/- 46 min. Urinary MHPG, corrected for creatinine levels, correlated with both 9 AM plasma MHPG and with baseline plasma MHPG. Furthermore, the relationship between plasma and urinary MHPG was linear when the rhythm of urinary levels was assumed to lag 6.2 hours behind the plasma rhythm. It was concluded that free MHPG is evenly distributed in the total body space and that conjugated MHPG is largely restricted to the blood.

Adult↗
PubMed1983

Evaluation of the safety and efficacy of bupropion in depression.

A placebo-controlled double-blind study was conducted to test the antidepressant effects of bupropion at dosage levels of 300 or 450 mg/day. Subjects were 30 hospitalized primary major depressives who were treated for 4 weeks. Physical and behavioral measures were obtained at baseline and at the end of each experimental week. The combined results of the two bupropion groups were significantly better than placebo. Preliminary results showed a significant antidepressant effect of the 300 mg/day dose, but not the 450 mg/day dose, compared to placebo. Anxiety symptoms were also somewhat reduced by the 300 mg/day dose. The results are compared with those of a previous study, which utilized higher dosages.

Adolescent↗
PubMed1983

Bupropion in depression: a tri-center placebo-controlled study.

In a double-blind, placebo-controlled, variable-dose study of 59 hospitalized nonpsychotic depressed patients, bupropion was significantly (p less than .05 to less than .001) more effective than placebo on measures of depression, anxiety, and global improvement. Statistically significant drug-placebo differences appeared as early as day 5 of treatment and increased on subsequent assessments. In an evaluation of Baseline X Treatment interactions, bupropion was particularly more effective than placebo in those patients with more severe depression. Placebo and bupropion groups had similar frequencies and severity of side effects. Laboratory data showed minimal differences between the two treatments. The most common adverse experience was mild dry mouth (20% of patients). Compared to placebo, bupropion was found to be effective in the treatment of depression and to have a favorable safety profile.

Adult↗
PubMed1983

Lithium therapy.

Explore the source record for details and available documents.

Bipolar Disorder↗
PubMed1982

Rat brain aryl acylamidase: further characterization of multiple forms.

1. Two fractions of aryl acylamidase (EC 3.5.1.13) were further separated from rat brain extracts at pH 7.5 by ammonium sulfate precipitation and Bio-Gel chromatography. 2. 1,2,3,4-Tetrahydro-beta-carboline competitively inhibited (67%) fraction-1 but slightly inhibited (13%) fraction-2. Tetrahydroharman, 6-hydroxy-tetrahydroharman and harminic acid slightly inhibited both fractions. Harmalol inhibited fraction-1 but enhanced fraction-2. 6-Methoxy-harman, 6-methoxy-harmalan and harmaline enhanced both fractions. 3. Pargyline did not affect either fraction. Methiothepin, cyproheptadine and chlorimipramine inhibited fraction-1 but stimulated fraction-2. 4. Neostigmine moderately (30%) inhibited AAA-2 but did not have any significant effect on AAA-1. 5. These results indicate that the beta-carboline compounds might play a role in regulating activity of AAA-1 and 2 in brain. 6. Both fractions might be related to serotonergic neurons but only AAA-2 might be associated with acetylcholinesterase.

Amidohydrolases↗
PubMed1982

The raphe neuronal system and serotonergic effects of LSD.

Earlier work from this laboratory had shown that LSD caused significant increases in rat brain serotonin (5-HT). The increase was later localized to a subsynaptosomal fraction consisting largely of synaptic vesicles. However, the source of the increase and the mechanism by which LSD caused the enhanced 5-HT binding or retention had not been elucidated. The present study was undertaken to evaluate the serotonergic effects of LSD following destruction of raphe nuclei with radiofrequency lesions. When LSD was given to animals with large midbrain raphe lesions, it caused significant increases in forebrain of cortical 5-HT up to 48 hr, or 7 days post-lesion, respectively. It was concluded that an intact cell body is not necessary for the expression of the LSD-mediated increases in 5-HT occurring in the nerve-ending. The possible mechanisms by which LSD could act directly at the nerve-ending are discussed.

Animals↗
PubMed1982

Nerve terminal effects of indoleamine psychotomimetics on 5-hydroxytryptamine.

The mode of action of indoleamine psychotomimetics has been closely linked to 5-HT. Early work showed increases in rat brain levels of 5-HT which were later localized to the nerve-ending fraction. With improved methodology, the 5-HT increment was further detected in the synaptic vesicle fraction. These effects were obtained with several indoleamine hallucinogens but not with mescaline. LSD has been most thoroughly studied and has served as the prototypical compound in ascertaining the mode of action of these drugs. Pretreatment with reserpine abolished the 5-HT effects of LSD in the vesicular fraction. However, a new compartment, termed "juxtavesicular," displayed 5-HT increases following reserpine and LSD. A soluble binding site for 5-HT within the synaptoplasm has been postulated in confirmation of independent results by other groups of investigators. The origin of the 5-HT increment appears to be associated with newly synthesized amine. This was deduced from experiments involving various 5-HT synthesis blockers. To ascertain whether inhibition of raphé neuronal firing is responsible for the accumulation of 5-HT at the nerve terminal, two sets of experiments were performed. Destruction of the raphé cell bodies by radiofrequency lesions failed to abolish the LSD-induced 5-HT increase early after the lesion. Destruction of cortical 5-HT neurons with the neurotoxin 5,7-dihydroxytryptamine completely abolished the 5-HT effect of LSD. It was concluded that an intact nerve terminal is necessary for the expression of the LSD-mediated increases in 5-HT. A LSD "autoreceptor" is postulated, possibly identical to a 5-HT presynaptic receptor inhibiting the release of 5-HT.

Amines↗
PubMed1982

Central cholinergic effects of tricyclic antidepressants in mouse.

The apparent rate of acetylcholine (ACh) turnover and levels of ACh and choline (Ch) in whole mouse brain were examined 30 min following i.p. injection of 25 mg/kg of three tricyclic antidepressants (TAD's): amitriptyline, chlorimipramine, and imipramine. The effects of these agents on high affinity choline uptake (HACU), a rate-limiting, regulatory step in ACh synthesis, were also examined. All three TAD's inhibited ACh turnover (by 27-40%), increased Ch levels (by 33-37%), and inhibited HACU (IC50's from 1.7 - 6.8 X 10(-5) M). Two of the three drugs produced significant decreases in ACh levels. It is concluded that these agents possess anticholinergic activity which is independent of their previously demonstrated muscarinic receptor blocking capabilities. As substantial evidence has accumulated linking increased cholinergic function with depression, it is speculated that this additional anticholinergic activity may contribute to the clinical efficacy of the TAD's.

Acetylcholine↗
PubMed1981

Noncompetitive amine uptake inhibition by the new antidepressant pridefine.

Pridefine (AHR-1118) is a pyrrolidine derivative with clinically established antidepressant efficacy. Previous work from this laboratory indicates that pridefine is a reuptake blocker of catecholamines and serotonin with weak releasing activity. This study characterized the mode of amine uptake inhibition by pridefine as noncompetitive. The uptake experiments were performed utilizing ouabain instead of zero-degree controls to differentiate between the passive and active components of uptake. Furthermore, the passive component was resolved into diffusion and binding of substrate. Correction was made for the effects of ouabain on binding. Kinetic constants determined from Lineweaver-Burk plots were: Km = 3 X 10(-7) M for NE, Km = 9 X 10(-8) M for DA, and Km = 3 X 10(-8) M for 5-HT. Dixon analyses of uptake at various pridefine concentrations indicated noncompetitive inhibition with Ki = 2.5 X 10(-6) M for NE uptake, Ki = 2.0 X 10(-6) M for DA uptake, and Ki = 1 X 10(-5) M for 5-HT uptake. These constants compare well IC50 values for the same transmitters: NE, IC50 = 2.4 X 10(-6) M; DA, IC50 = 2.8 X 10(-6) M; 5-HT, IC50 = 1.0 X 10(-5) M. The in vitro results indicate that pridefine is relatively specific as a catecholamine uptake blocker. It differs from tricyclic antidepressants which are reportedly competitive inhibitors of monoamine uptake. The possible mechanisms by which pridefine acts as a noncompetitive inhibitor are discussed.

Animals↗
PubMed1980

Compartmentation of catecholamines in rat brain: effects of agonists and antagonists.

The subsynaptosomal distributions of dopamine (DA) in striatum and of norepinephrine (NE) in hypothalamus and cerebral cortex were examined. Isolated nerve-endings from each region were osmotically disrupted and subfractionated into a soluble cytoplasmic fraction (end supernatant, Se) and a synaptic vesicle fraction (P2V). DA and NE were measured in the crude homogenate and in subcellular fractions by a radioenzymatic assay. Levels of NE and DA were 3--5 times higher in the nerve-ending cytoplasm than in the synaptic vesicles, suggesting that catecholamines within the nerve-endings are predominantly in soluble form. Amphetamine increased DA levels in the tissue homogenate and in the nerve-ending cytoplasm but not in synaptic vesicles. Pargyline and gamma-butyrolactone (GBL) increased DA levels in all fractions with the greatest increase occurring in the cytoplasmic fraction. Both 6-hydroxydopamine (6-OHDA) and alpha-methyltyrosine (AMT) caused uniform DA decreases in all fractions. Hypothalamic levels of NE in the two nerve-ending compartments were also reduced to a similar extent after AMT. Reserpine produced uniform depletions of striatal DA in both nerve-ending fractions while the rate of DA repletion was more rapid in the vesicular compartment. Levels of hypothalamic NE were also uniformly depleted by reserpine at the times examined. The cytoplasmic storage compartment is discussed in terms of a possible anatomical correlate such as the smooth endoplasmic reticulum.

4-Butyrolactone↗