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Biomedical subjects

D E Redmond

Publications and source records attributed to D E Redmond.

At least 91 records · Page 5Linked to original sources
PubMed1985

Precipitated diazepam withdrawal elevates noradrenergic metabolism in primate brain.

Following treatment for seven days with diazepam (2.0 mg/kg i.m., b.i.d.), administration of the benzodiazepine receptor antagonist RO 15-1788 (5 mg/kg) induced a severe withdrawal syndrome in vervet monkeys which included tremors, vomiting, vocalizations, chewing, and piloerection. Brain concentrations of the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly higher in the precipitated withdrawal group than in the diazepam plus vehicle control group. Administration of RO 15-1788 without prior diazepam treatment had no effect on brain MHPG, nor did it produce withdrawal behaviors, but did produce an increase in the frequency of scratching. These results raise the possibility that increased central noradrenergic activity serves a role in benzodiazepine withdrawal similar to the role hypothesized for noradrenergic activity in opiate withdrawal.

Animals↗
PubMed1985

Somatic symptoms in primary affective disorder. Presence and relationship to the classification of depression.

The incidence and severity of somatic symptoms were determined in 132 patients with major depressive disorder and 80 normal controls. The role of somatic symptoms was analyzed in relation to the unipolar-bipolar division, Research Diagnostic Criteria (RDC) subtypes, hypersomnia, and appetite increase. The data suggest that the rate and level of somatic symptoms increased with the severity of depression and age, only appetite loss differentiated unipolar from bipolar patients, and the classic somatic symptoms of depression were present in most RDC subtypes and not exclusively associated with the "endogenous" subtype. Hypersomnia or increased appetite identified two overlapping depressive subgroups; patients in both groups were young and characterized by high interpersonal sensitivity. Hypersomniac depressed patients were less anxious and agitated; patients with increased appetite were more hostile and showed a greater decrease in libido than age-matched and sex-matched patients with neither symptom.

Adult↗
PubMed1985

Depressive behavior and hyperactive adrenocortical function.

This study examined relationships between depressive subtypes, clinical-behavioral characteristics, and hypothalamic-pituitary-adrenocortical (HPA) function in 132 hospitalized depressed patients. There were significant positive correlations between several pre- and postdexamethasone plasma cortisol measures and anxiety, psychomotor disturbance, distressed expression, and sleep disturbance. Few significant relationships were seen between illness severity and HPA function. Virtually no endocrine differences were seen between endogenous and nonendogenous subtypes or between psychotic and nonpsychotic subtypes. These results and the previous literature suggest a profile of depressed patients with HPA overactivation; they are likely to be anxious, to have sleep and psychomotor disturbances, to have lost weight in the current episode, and to be older.

Adrenal Cortex↗
PubMed1984

Naltrexone precipitated opiate withdrawal in methadone addicted human subjects: evidence for noradrenergic hyperactivity.

The noradrenergic alpha-2 receptor agonist, clonidine, suppresses many of the effects of opiate withdrawal in both humans and other animals and this is consistent with the data indicating important interactions of opiate and noradrenergic systems in brain. This evidence supports the hypothesis that central noradrenergic hyperactivity is involved in the expression of major signs and symptoms of the opiate withdrawal syndrome, but to date clinical studies have not provided biochemical data consistent with this idea. In order to assess whether naltrexone precipitated opiate withdrawal in methadone addicted human subjects is associated with changes in noradrenergic function, a double-blind study was completed in which 15 methadone-dependent subjects received naltrexone and 8 subjects received placebo. Signs and symptoms of the opiate abstinence syndrome increased significantly in the 15 subjects who received naltrexone compared with the 8 who received placebo. Plasma concentrations of free MHPG also increased significantly in those subjects who took naltrexone compared to the placebo treated subjects. In addition, withdrawal signs and symptoms were significantly correlated with plasma MHPG concentration. Since several compounds which suppress central noradrenergic activity also reduce the severity of the withdrawal syndrome, the noradrenergic hyperactivity suggested by the present clinical study may be a functional mechanism for at least part of the opiate withdrawal syndrome.

Adult↗
PubMed1984

Neuronal activity of the locus ceruleus in awake Macaca arctoides.

Neuronal activity in the locus ceruleus of awake, behaving stump-tailed monkeys increased consistently and vigorously after presentation of mildly aversive and threatening stimuli. These preliminary data increase the range of stimuli reported to elicit locus ceruleus activity in awake monkeys to include nonpainful threat signals and suggest that more studies are needed to be able to categorize locus ceruleus function from its unit activity responses.

Acoustic Stimulation↗
PubMed1983

Yohimbine induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine.

Yohimbine (30 mg) produced significant increases in subjective anxiety, autonomic symptoms, blood pressure, and plasma 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) in ten healthy subjects. The effects of pretreatment with diazepam (10 mg) or clonidine (5 micrograms/kg) on these yohimbine induced changes was examined. Both diazepam and clonidine significantly antagonized yohimbine-induced anxiety, but only clonidine significantly attenuated the yohimbine induced increases in plasma MHPG, blood pressure, and autonomic symptoms. When given alone, clonidine significantly decreased plasma MHPG and blood pressure, whereas diazepam did not. These findings indicate that: (1) noradrenergic hyperactivity may be a factor in the production of some anxiety states; (2) the anti-anxiety effects of clonidine appear to result from its actions on receptors which decrease noradrenergic activity; (3) diazepam reverses yohimbine-induced anxiety without effects on several physiological or biochemical indicators of noradrenergic activity in humans.

Adult↗
PubMed1983

Panic-induced elevation of plasma MHPG levels in phobic-anxious patients. Effects of clonidine and imipramine.

Six subjects with the phobic-anxiety syndrome were treated in a controlled, crossover trial of clonidine hydrochloride v imipramine hydrochloride for periods of four weeks each. During each drug trial and during baseline placebo treatment, each patient exposed himself or herself to a situation that previously elicited panic attacks. Self-rated anxiety and plasma levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured to study the effect of the drug treatments on noradrenergic activity and anxiety. Plasma MHPG level correlated highly with rated anxiety under all conditions, and was consistent with significant symptom reduction by clonidine or imipramine. Diminished suppression of plasma MHPG concentrations in two subjects was associated with the continued emergence of panic symptoms in response to phobic stimuli.

Adult↗
PubMed1983

Neurobiological mechanisms in human anxiety. Evidence supporting central noradrenergic hyperactivity.

Preclinical studies in laboratory rodents and non-human primates have led to the hypothesis that noradrenergic hyperactivity is associated with some human anxiety states. This hypothesis has recently received support from a variety of clinical investigations. Drugs which increase noradrenergic function induce anxiety in human subjects. Increased turnover of norepinephrine has been shown to occur with naturally occurring anxiety conditions. The mechanism of action clonidine and tricyclic antidepressants as antianxiety agents may be due to their ability to reduce central noradrenergic function. Future studies will need to evaluate, in addition to central noradrenergic function, other neuronal systems in brain involving endogenous opioids, benzodiazepine receptors, purines and gamma-aminobutyric acid in human anxiety disorders.

Animals↗
PubMed1983

A preliminary description of acute physical dependence on morphine in the vervet monkey.

Previous animal studies have suggested the rapid development of opiate dependency in 24 hours or less. However, the development of dependence on opioids within twenty-four hours has yet to be demonstrated in previously opiate-free human or nonhuman primate subjects. Following naloxone administration, cable-restrained monkeys which received intravenous morphine hourly for only six hours exhibited a behavioral syndrome characteristic of opioid withdrawal in this particular species. These data indicate that acute physical dependence on morphine may be induced after six hours in a primate species.

Animals↗
PubMed1983

Relative importance of 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol as norepinephrine metabolites in rat, monkey, and humans.

A gas chromatographic-mass spectrometric assay, which allowed simultaneous measurement of 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG), was used to show that the concentration of MHPG in primate CNS far exceeded that of DHPG and that both metabolites were mainly in the unconjugated form. In rat brain, DHPG concentration was generally higher than that of MHPG, and both existed predominantly as conjugates. Rat and primate plasma contained more MHPG than DHPG. In plasma of primates but not of rats, higher proportions of the metabolites were conjugated, compared to those in brain. Significant correlations existed between MHPG and DHPG in rat brain, monkey brain, human plasma, and both monkey CSF and plasma. In monkeys, a significant CSF-plasma correlation was found for MHPG, but not for DHPG. Acute administration of piperoxane raised rat brain MHPG and DHPG concentration; desipramine prevented this rise in DHPG, but not in MHPG. Desipramine alone decreased DHPG, but not MHPG, concentration. Piperoxane increased monkey brain MHPG, but not DHPG, concentration. These data suggest that DHPG is a valuable metabolite to measure when assessing norepinephrine metabolism in the rat. Under certain conditions, measurement of rat brain MHPG and DHPG may provide information concerning the site of norepinephrine metabolism. However, in primates the importance of monitoring DHPG, in addition to MHPG, is uncertain.

Animals↗
PubMed1983

Spontaneous ejaculation associated with anxiety: psychophysiological considerations.

The association of anxiety with sexual excitement has been noted since the early part of this century. The authors present case reports of a schizophrenic and a neurotic patient in whom no direct sexual precipitants of spontaneous ejaculation could be identified but in whom severe anxiety was evident. The central noradrenergic neurophysiology that anxiety may share with sexual excitement could provide a basis for spontaneous ejaculation during anxiety. The pharmacology of spontaneous ejaculation during opiate withdrawal is used to elaborate this central noradrenergic model.

Adult↗
PubMed1982

Brain catecholamine metabolites and behavior in morphine withdrawal.

Morphine withdrawal behavior, brain and plasma catecholamine metabolites, and brain beta-noradrenergic receptor binding were examined after acute treatment with naloxone in rats treated with morphine pellets or a sham pelleting procedure. Increases in brain 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), a norepinephrine metabolite, occurred in parallel with rated withdrawal behavior. Withdrawal behavior correlated significantly with brain, and, more modestly, with plasma levels of MHPG but did not correlate with beta-receptor binding or HVA. The effectiveness of debrisoquin sulfate was variable, but the reductions in withdrawal signs and cerebral cortex MHPG were strongly correlated. These data support a direct relationship between presynaptic noradrenergic hyperactivity and opiate withdrawal behavior.

Animals↗
PubMed1982

Methylxanthine activation of noradrenergic unit activity and reversal by clonidine.

Methylxanthines increase central noradrenergic turnover by an unknown mechanism. Isobutyl methylxanthine (IBMX, 0.5-16 mg/kg i.v.) was found in this study to increase firing rats of noradrenergic neurons in the locus coeruleus, supporting increased impulse flow as one possible mechanism for increased noradrenergic turnover. Naloxone (1 mg/kg i.p.) pretreatment potentiated the effects of IBMX, while clonidine (0.01 mg/kg i.v.) reversed increases in activity. Some of the behavioral effects of methylxanthines are consistent with increased noradrenergic activity.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Plasma and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) as indices of brain norepinephrine metabolism in primates.

The relationship between MHPG concentration in several brain areas, cisternal CSF and plasma was examined in 26 vervet monkeys. Free MHPG was measured by gas chromatography-mass spectrometry using deuterated MHPG as internal standard. In animals with or without treatment with drugs that alter norepinephrine metabolism, highly significant correlations were found in concentrations of MHPG between the various brain areas, between plasma and CSF, between plasma and brain areas and between CSF and brain areas. The concentration of MHPG in CSF was higher than in plasma and with the exception of occipital cortex, all brain regions contained a higher concentration of MHPG than CSF. This study supports the notion that free MHPG concentrations in plasma and cisternal CSF are useful indices of central noradrenergic activity.

Animals↗
PubMed1982

Clonidine and naltrexone. A safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy.

Clonidine hydrochloride and naltrexone hydrochloride, given in combination, were found to provide a safe, effective, and extremely rapid treatment of abrupt withdrawal from methadone hydrochloride therapy. Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, ten (91%) of 11 patients were able to withdraw completely from methadone therapy by the end of a six-day period. Six days of clonidine hydrochloride treatment, with a peak mean dose of 2.9 mg/day on treatment day 2, attenuated the withdrawal-inducing effects of naltrexone. Naltrexone hydrochloride was gradually increased from an initial 1-mg dose on treatment day 2 to 50-mg maintenance dose on treatment day 5 without an associated increase in withdrawal symptoms. Clonidine significantly decreased BP without producing clinical problems. The withdrawal symptoms of anxiety, restlessness, and muscular aching were most resistant to treatment, but at discharge most patients were completely asymptomatic.

Adult↗
PubMed1982

Clonidine suppresses methylxanthine induced quasi-morphine withdrawal syndrome.

The effects of the alpha-2 adrenergic agonist, clonidine, on the "quasi-morphine withdrawal syndrome" (QMWS) were examined in drug naive rats. The QMWS was induced by combined systemic administration of iso-butyl-methylxanthine (IBMX: 15 mg/kg, IP) and naloxone (1 mg/kg, IP). Pretreatment with clonidine (50 micrograms/kg, IP) significantly decreased the incidence of 11 out of 16 withdrawal signs. Since clonidine suppresses signs and symptoms of true morphine withdrawal, the suppression of methylxanthine effects demonstrates an additional similarity of the QMWS to true morphine withdrawal. These results suggest that a significant common neural mechanism of both the QMWS and true morphine withdrawal is affected by clonidine.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Pre-treatment neurotransmitter metabolites and response to imipramine or amitriptyline treatment.

Preliminary data are presented from the NIMH Collaborative Study on the psychobiology of depression, biological studies, dealing with relationships between the pre-treatment levels of the neurotransmitter metabolites 3-methoxy-4-hydrophenethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and the subsequent therapeutic response of depressed patients to imipramine or amitriptyline. Eighty-seven depressed patients were studied during pre-treatment and treatment periods. It has been found that (1) both low pre-treatment urinary MHPG and low CSF 5-HIAA values are associated with a response to imipramine; these relationships were not artefacts due to sex or age; (2) there were no significant relationships between pre-treatment urinary MHPG, CSF MHPG, 5-HIAA, or HVA values and the subsequent response, or failure of response, to amitriptyline; (3) there was not a bimodal distribution for CSF 5-HIAA. For both males and females, there were positive and statistically significant correlations between CSF MHPG and urinary MHPG; for the females, there were positive and significant correlations between both urinary and CSF MHPG and CSF 5-HIAA. The theoretical and practical implications of these findings are discussed.

Amitriptyline↗