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Biomedical subjects

D L Murphy

Publications and source records attributed to D L Murphy.

At least 361 records · Page 20Linked to original sources
PubMed1984

Interactions of phencyclidine with crayfish muscle membranes. Sensitivity to calcium channel antagonists and other drugs.

[3H]Phencyclidine ( [3H]PCP) bound to crayfish abdominal muscle membranes at pH 7.4 with two affinities (Kd of 0.96 nM for 0.38 pmole/mg of protein, and 18.9 nM for 7.6 pmoles/mg of protein). Binding affinities increased at higher pH, suggesting that binding may be due mostly to the un-ionized form of [3H]PCP. This high-affinity [3H]PCP binding was sensitive to the actions of trypsin, protease, and dicyclohexylcarbodiimide, but insensitive to phospholipase A, concanavalin A,N-ethylmaleimide, and dithiothreitol. Calcium channel antagonists were most potent in inhibiting the high-affinity [3H]PCP binding with the following descending order of potencies: bepridil greater than nicardipine = diltiazem = verapamil greater than cinnarizine greater than (+)-D-600 greater than (-)-D-600 greater than 4-NO2-nifedipine greater than 2-NO2-nifedipine. The binding was also highly sensitive to several PCP analogues, antipsychotics, piperocaine , and tilorone, and moderately sensitive to d-tubocurarine, atropine, imipramine, nortryptyline , and tetracaine. Although verapamil and nifedipine inhibited the action potential of crayfish muscle, PCP did not and actually prolonged slightly the falling phase of the action potential. Although it is unlikely that the [3H]PCP binding protein in crayfish muscles is a Ca2+ channel, it is possible that it may be a K+ channel.

Action Potentials↗
PubMed1984

Monoamine oxidase-inhibiting antidepressants. A clinical update.

This article outlines the latest information on the clinical efficacy of MAOIs and provides the physician with guidelines for their safe use. The important side effects of this class of drugs are also summarized along with an up-to-date account of their possible molecular mechanism of action.

Antidepressive Agents, Tricyclic↗
PubMed1984

Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man.

Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.

Carbidopa↗
PubMed1984

New contributions from basic science to understanding the effects of monoamine oxidase inhibiting antidepressants.

Recent studies have provided almost conclusive evidence for the existence of the two separate MAO isozymes previously postulated to exist on the basis of indirect evidence. Important differences in the proportions and distribution of these two enzyme forms across species and in various tissues are responsible for some puzzling anomalies in earlier studies and contribute to differences in behavioral responses, blood pressure changes, and toxic responses to tyramine and other sympathomimetic agents. Substrate-selective, irreversible inhibitors, as well as several new classes of reversible MAO-A and MAO-B selective inhibitors, may provide a spectrum of clinical effects different from the nonselective irreversible MAO inhibitors.

Animals↗
PubMed1984

High dose naloxone in depression.

The behavioral effects of a 2 mg/kg iv bolus infusion of naloxone were compared with a placebo infusion using a double-blind design in a small group of inpatient depressives (n = 6) and normals (n = 8). Naloxone produced consistent and significant worsening in the rated signs and subjective symptoms of depression in the patients. In the normals, lesser changes in Hamilton depression and BPRS total scores were observed while none of the subjective scales were significantly altered. The data suggest that depressives manifest a more marked and subjectively more intense response to naloxone compared to normals. Further studies are required to confirm this preliminary finding and to clarify its relationship to the pathogenesis of depression.

Adult↗
PubMed1983

Long-term clorgyline treatment antagonizes the eating and motor function responses to m-chlorophenylpiperazine.

Treatment for 21 days but not 3 days with clorgyline, a selective monoamine oxidase type A inhibitor with antidepressant effects, causes significant escape from m-chlorophenylpiperazine's effects on food intake, sedation level and induction of limb movements, but sensitizes rats to ejaculation. These findings support the prior reports of functional serotonin pathway adaptational changes in the motor system in response to antidepressant treatment and extend these findings to serotonin pathways involved in eating behavior.

Animals↗
PubMed1983

Light and propranolol suppress the nocturnal elevation of serotonin in the cerebrospinal fluid of rhesus monkeys.

Markedly elevated nighttime concentrations of serotonin in rhesus monkey cerebrospinal fluid were reduced to daytime levels by exposing the monkeys to continuous light or to the beta-adrenergic antagonist propranolol. Nighttime elevations of melatonin in cerebrospinal fluid were also suppressed by propranolol and light. Serotonin released in large quantities at night appears to be regulated like melatonin, and may act as a cerebroventricular hormone to influence brain and pituitary function at night.

Animals↗
PubMed1983

Self-stimulation responses are altered following long-term but not short-term treatment with clorgyline.

Clorgyline (a selective monoamine oxidase-inhibiting antidepressant) given chronically facilitated hypothalamic self-stimulation in rats, while acute treatment was without effect. Furthermore, long-term but not short-term clorgyline treatment significantly attenuated the suppressive effect of the selective alpha 2-adrenergic agonist clonidine on this behavior. These findings suggest that adaptative alterations in the modulation of rewarded behavior by inhibitory presynaptic noradrenergic receptors may be involved in antidepressant efficacy.

Animals↗
PubMed1983

Interaction between cytosolic monoamine oxidase and spin-labeled amphetamine and its modification by clorgyline and pargyline.

Interactions between a monoamine oxidase (monoamine: oxygen oxidoreductase deaminating, EC 1.4.3.4) obtained from rat liver cytosol by high speed centrifugation and a biologically active, spin labeled analog of amphetamine have been analyzed. The acetylenic monoamine oxidase inhibitors, pargyline and clorgyline, have been used to modulate the binding of spin labeled amphetamine. Broadening of electron spin resonance lines induced by immobilization of the probe on binding has been used to determine the concentration of bound probe. Pargyline was found to inhibit binding of spin labeled amphetamine by cytosolic monoamine oxidase. Bound spin labeled amphetamine was also displaceable by pargyline. In contrast, clorgyline enhanced the binding of spin labeled amphetamine to the cytosolic monoamine oxidase preparation. Inhibition or enhancement of amphetamine binding was very rapid and occurred during the reversible stage of interaction between the enzyme and the acetylenic compounds.

Amphetamine↗
PubMed1983

Obsessive-compulsive disorder. A double-blind trial of clomipramine and clorgyline.

Patients with obsessive-compulsive disorder who met DSM-III criteria and who had been ill for at least one year were studied in a double-blind, randomized, crossover comparison of the tricyclic antidepressant clomipramine hydrochloride and the monoamine oxidase inhibitor clorgyline hydrochloride. No significant improvement was evident after four weeks of treatment with placebo prior to the crossover study. Treatment with clomipramine was associated with significant improvement after both four and six weeks in measures of obsessions, anxiety, and depression. Antiobsessional responses to clomipramine did not depend on presence of depression. Improvement was correlated with plasma concentrations of clomipramine, but not with the plasma concentrations of any of its metabolites. No significant improvement was evident for the entire group with clorgyline treatment, although the conditions of individual patients did respond to the drug.

Adult↗
PubMed1983

High-dose naloxone infusions in normals. Dose-dependent behavioral, hormonal, and physiological responses.

Hypotheses of involvement of the endogenous opioid system (EOS) in the regulation of human behavior suggest that functional blockade of the EOS should have behavioral consequences. Clinical administration of the opiate receptor antagonist naloxone hydrochloride, however, has had little or inconsistent behavioral effects in normals. This may be attributable to the use of doses insufficient to yield a complete EOS blockade. To assess this explanation, normals were administered increasing doses of naloxone hydrochloride (0.3 to 4 mg/kg) in a single-blind design. Significant dose-dependent behavioral, hormonal, and physiological effects were found. With increasing doses of naloxone, volunteers demonstrated increasingly dysphoric affects, a deterioration of performance on memory testing, increasing systolic BP and respiratory rate, and increasing plasma cortisol and growth hormone levels. These results are consistent with the expected effects of increasing EOS blockade, and thus suggest that lower doses of naloxone used in previous clinical studies may not have been sufficient to produce a complete EOS blockade. Specifically, they suggest involvement of the EOS in the tonic regulation of normal human mood, memory, BP, respirations, and plasma growth hormone and cortisol levels.

Adult↗
PubMed1983

D-amphetamine in obsessive-compulsive disorder.

In a double-blind crossover study, single doses of d-amphetamine and placebo were administered to 12 patients with severe chronic obsessive-compulsive disorder (OCD). Improvement of obsessional symptoms was significant on clinical ratings and was correlated with improved performance on an attention task. Changes were also significant for self-rated measures of activation and altered reality. The behavior response to amphetamine was not statistically correlated with subsequent improvement during a 6-week clomipramine trial, although the direction of change was the same during both treatments for every patient studied.

Adolescent↗
PubMed1983

A morphometric analysis of ischemic canine myocardium with and without reperfusion.

Progressive morphological changes have been quantitated in ischemic and control regions of canine hearts previously assessed biochemically and physiologically. Muscle strips removed after a 5 or 10-min occlusion of the left circumflex artery were compared to those removed after reperfusion for 20 or 60 min following 10 min occlusion and to those removed immediately from normal and sham-operated dogs. Decreased glycogen content and decreased mitochondrial matrix were observed in fibers from ischemic regions as early as 5 min after ligation. Changes in the mitochondrial volume fraction were calculated by the point counting method and changes in the number of lipid droplets per unit area were determined. Mitochondrial volume fractions in ischemic regions were not significantly higher when compared to control regions of the same hearts, and were similar to the values measured for 10 and 70-min sham-operated dogs. We conclude that in early acute ischemia considerable variability in the different control groups emerges with extensive sampling and must be considered in interpreting ultrastructural changes.

Animals↗
PubMed1983

Effect of long-term clorgyline administration on human platelet alpha-adrenergic receptor binding and platelet cyclic AMP responses.

Platelet alpha 2-adrenergic receptor number and physiologic responsiveness, as well as plasma norepinephrine (NE), were evaluated in psychiatric patients with major depressive disorder before and during chronic clorgyline treatment. The alpha 2-adrenergic receptor number was determined by measuring the binding of tritiated dihydroergocriptine (3H-DHE) to platelet membranes. Physiologic responsiveness was determined by measuring the response of cyclic adenosine 3'-5'-monophosphate (cAMP) to prostaglandin E1 (PGE1), and the inhibition of the PGE1-stimulated cAMP response by NE in intact platelets. No significant differences from pretreatment values were observed in platelet alpha 2-adrenergic binding or responsiveness during clorgyline treatment. Baseline platelet cAMP production and plasma NE levels were significantly decreased after chronic clorgyline treatment. Previous studies on animals and humans have suggested that brain alpha 2-adrenergic receptor responsiveness decreases during chronic clorgyline treatment. The present findings therefore suggest that such changes may represent adaptations induced by long-term clorgyline administration which may differ between the brain and the platelet, thus illustrating potential limitations of the study of platelet alpha 2-adrenergic receptors as a model for central alpha 2-adrenergic receptor adaptation.

Adult↗
PubMed1983

High-dose naloxone affects task performance in normal subjects.

Increasing intravenous doses of naloxone (0.3 mg/kg, 1 mg/kg, and 2 mg/kg) were administered to normal subjects. Naloxone at 2 mg/kg, but not at lower doses, impaired aspects of memory as measured by a verbal learning task which assessed the direct free recall and recognition of presented versus non-presented words of a single category (effortful processing) and the monitoring of the frequency of such presentations (automatic processing). At the same time "working" memory was left unaffected. The results suggest a role for the opioid system in some memory processes in man.

Adult↗
PubMed1983

Clinical studies of monoamine receptors in the affective disorders and receptor changes with antidepressant treatment.

Pre-clinical and clinical studies suggest that the responsiveness of monoamine and cholinergic receptors may be altered in the affective disorders and that antidepressants may modify the sensitivity of these receptors. The growth hormone response to clonidine is reduced in depressed patients compared to controls according to several independent studies, suggesting that post-synaptic alpha 2-adrenergic receptors may be less responsive in depressed patients. The cortisol response to clonidine is enhanced in depressed patients compared to controls in our study raising the possibility that cortisol hypersecretion in depressed patients may be related to noradrenergic dysfunction. The hypotensive response to clonidine is blunted in patients on chronic antidepressant treatment with either clorgyline or desipramine suggesting that pre-synaptic alpha 2-adrenergic receptors may subsensitize with chronic antidepressant treatment. The prolactin increase in response to fenfluramine is less in depressed patients compared to controls suggesting decreased functional activity of the serotonergic system in depression. Platelet alpha 2-adrenergic receptor number as measured by tritiated dihydroergocriptine (3H-DHE) binding is increased in depressed patients compared to controls, while cyclic 3'-5' adenosine monophosphate (cAMP) production in response to prostaglandin E1 (PGE1) and norepinephrine (NE) inhibition of PGE1-stimulated cAMP production are reduced in the platelets of depressed patients. Thus, it is not clear that increased 3H-DHE binding reflects increased functional responsiveness and might in fact be compensatory to decreases in functional responses of alpha 2-adrenergic receptors.

Clonidine↗