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Biomedical subjects

D L Murphy

Publications and source records attributed to D L Murphy.

At least 217 records · Page 12Linked to original sources
PubMed1991

Differential effects of antidepressant treatments on fenfluramine-induced increases in plasma prolactin and corticosterone in rats.

Intravenous administration of 5-HT releasing agent, fenfluramine, to rats produced increases in plasma prolactin and corticosterone concentrations. Short-term or long-term treatment with either clorgyline or imipramine did not affect baseline levels of prolactin or corticosterone. On the other hand, short-term but not long-term lithium treatment significantly increased baseline levels of corticosterone but not of prolactin. Short-term treatment with lithium but not clorgyline or imipramine potentiated fenfluramine-induced increases in plasma prolactin but not corticosterone. On the other hand, long-term treatment with clorgyline but not imipramine or lithium attenuated fenfluramine's effect on plasma prolactin but not on corticosterone. These findings demonstrate differential effects of antidepressant treatments on fenfluramine-induced increases in plasma prolactin and corticosterone in rats and are consistent with several other clinical and animal studies demonstrating dissimilar actions of different antidepressant treatments on two different 5-HT-mediated neuroendocrine functions.

Animals↗
PubMed1991

Plasma catecholamines and their metabolites in obsessive-compulsive disorder.

Plasma catecholamines and their metabolites were sampled in 13 medication-free patients with obsessive-compulsive disorder (OCD) and 29 normal controls. In addition to severe OCD symptoms, the patients had significantly higher anxiety, tension, and resting pulse rates than the controls. Nonetheless, mean plasma concentrations of norepinephrine (NE) and epinephrine (E), the catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA), and the stress-related hormone cortisol did not differ between OCD patients and normal controls. When the patients and control populations were combined and average plasma NE and E levels calculated over 35 min, subjects with a higher mean NE output (greater than 1.1 pm/ml) had higher Profile of Mood States depression scores than subjects with a low NE output (less than 1.1 pm/ml). Altogether, these results indicate that elevated plasma catecholamine measures are not likely to be associated with the pathophysiology of OCD.

Adult↗
PubMed1991

Controlled comparison of buspirone and clomipramine in obsessive-compulsive disorder.

Eighteen outpatients with obsessive-compulsive disorder were treated with either buspirone, a partial serotonin agonist, or clomipramine, a serotonin uptake inhibitor, in a double-blind, random-assignment study. Both drugs led to statistically significant and similar improvements in scores on the Yale-Brown Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression scales. This preliminary result warrants further exploration with a larger sample and other serotonergic agents.

Adult↗
PubMed1991

Symptoms of eating disorders in patients with obsessive-compulsive disorder.

OBJECTIVE: This study was designed to explore potential overlap of the symptoms of obsessive-compulsive disorder and eating disorders. METHOD: The authors administered a structured, self-rating scale, the Eating Disorder Inventory, to 59 outpatients at an obsessive-compulsive disorder clinic and to 60 sex-matched normal volunteers. The Eating Disorder Inventory has been previously validated as a reliable measure of the specific cognitive and behavioral dimensions of the psychopathology typical of patients with eating disorders. The scores of the patients with obsessive-compulsive disorder and of the healthy comparison subjects were compared with those of 32 female inpatients with anorexia nervosa (N = 10) or bulimia nervosa (N = 22) who had also been given the inventory. RESULTS: The patients with obsessive-compulsive disorder scored significantly higher than the healthy comparison subjects on all eight subscales of the Eating Disorder Inventory: drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears. Relative to the healthy subjects, male patients with obsessive-compulsive disorder had more symptoms than female patients with obsessive-compulsive disorder. The scores of the female patients with obsessive-compulsive disorder were midway between those of the 32 female patients with eating disorders and those of the 35 female normal subjects. CONCLUSIONS: These results suggest that patients with obsessive-compulsive disorder display significantly more disturbed eating attitudes and behavior than healthy comparison subjects and that they share some of the psychopathological eating attitudes and behavior that are common to patients with eating disorders.

Adult↗
PubMed1991

A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder.

In this study, 16 patients with obsessive-compulsive disorder (OCD) who had partially improved during at least 6 months of treatment with clomipramine were sequentially treated with triiodothyronine and lithium carbonate in an 8-week double-blind cross-over study. Both triiodothyronine and lithium carbonate have been reported to be efficacious in open trials as adjunctive agents when combined with tricyclics in the treatment of OCD and depressed patients. However, in our controlled study, OCD and depressive symptoms, as assessed by standardized rating scales in the patient group as a whole, did not significantly change after either adjuvant treatment. Further analysis on an individual patient basis revealed that neither adjuvant medication was associated with a clinically meaningful change (greater than 25%) in OCD symptoms. However, lithium, but not triiodothyronine, adjuvant therapy was associated with a 25% or greater reduction in depression scores in 44% of the patients. This controlled study lends further support to the contention that OCD may represent a disorder with characteristics distinct from affective disorders.

Adult↗
PubMed1991

Abnormal protein in the cerebrospinal fluid of patients with a submicroscopic X-chromosomal deletion associated with Norrie disease: preliminary report.

Norrie disease is an X-linked recessive disorder characterized by congenital blindness and, in many cases, mental retardation. Some Norrie disease cases have been shown to be associated with a submicroscopic deletion in chromosomal region Xp11.3. Cerebrospinal fluid (CSF) was collected from four male patients with an X-chromosomal deletion associated with Norrie disease. CSF proteins were resolved using two-dimensional gel electrophoresis and then analyzed by computer using the Elsie V program. Our analysis revealed a protein that appears to be altered in patients with Norrie disease deletion.

Blindness↗
PubMed1990

Beta-endorphin responses to different serotonin agonists: involvement of corticotropin-releasing hormone, vasopressin and direct pituitary action.

Activation of serotonergic neurotransmission has been shown to increase plasma beta-endorphin-like immunoreactivity (beta-End-LI). To study the mechanism(s) of this action, we measured the effects of 3 potent serotonin (5-HT) agonists with different structures and 5-HT receptor binding profiles in conscious unrestrained Sprague-Dawley rats in vivo and in dispersed anterior pituicytes in vitro. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), all markedly increased beta-End-LI in plasma in vivo. All 3 responses were blocked by dexamethasone pretreatment. Pituitary stalk transection (PST), as well as pretreatment with rabbit serum hyperimmune against rat corticotropin-releasing hormone (CRH, TS-6) completely abolished beta-End-LI response to 8-OH-DPAT and attenuated the responses by about 60% to DOI. Responses to m-CPP were markedly attenuated in PST rats, but pretreatment with TS-6 had no significant effect. To examine whether vasopressin (AVP) might be involved in the CRH neutralizing antibody-resistant beta-End-LI responses after m-CPP and DOI, we measured AVP concentrations after each agonist, m-CPP, but not DOI or 8-OH-DPAT, significantly elevated circulating AVP levels. As a proof of direct pituitary effect, DOI markedly stimulated beta-End-LI release from the anterior pituitary cell culture preparation in vitro. It was approximately as potent as CRH in the picomolar range, m-CPP was much less effective than DOI, while 8-OH-DPAT did not stimulate beta-End-LI release in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Effects of daily oral m-chlorophenylpiperazine in elderly depressed patients. Initial experience with a serotonin agonist.

Six patients (mean age 62.5 +/- 7.6 years) with major depression were treated for 2 weeks with the serotonin agonist m-chlorophenylpiperazine (m-CPP), 80 mg/day in a double-blind, placebo-controlled, crossover-design pilot study. Two patients showed clinically significant improvement in depressive symptoms during active drug treatment, whereas two others showed modest effects. All patients tolerated the drug, with no major side effects and no changes in vital signs or in liver, renal, thyroid, or hematological function. Further studies are needed to determine the characteristics of the possible antidepressant effects of m-CPP; such work may yield greater understanding of the role of serotonin in affective and other psychiatric disorders.

Aged↗
PubMed1990

Carbamazepine and electroconvulsive shock attenuate beta-adrenoceptor and muscarinic cholinoceptor coupling to G proteins in rat cortex.

We have recently found that lithium attenuates the function of G proteins, suggesting these proteins as the common site for both the antimanic and antidepressant therapeutic effects of lithium. Perturbation of G protein function may thus be a general characteristic of treatments effective in bipolar affective disorder. In the present study, we demonstrate that both chronic carbamazepine and repeated electroconvulsive shock treatment inhibit the coupling of both muscarinic cholinoceptors and beta-adrenoceptors to pertussis toxin-sensitive and cholera toxin-sensitive G proteins, respectively.

Animals↗
PubMed1990

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine.

In a recent study, we reported abnormal local cerebral glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive disorder. Eight patients with obsessive-compulsive disorder scanned previously were scanned again during treatment with the tricyclic antidepressant clomipramine hydrochloride. Comparisons of local cerebral glucose metabolic rates for both groups showed a relative decrease in regions of the orbital frontal cortex and the left caudate, and an increase in other areas of the basal ganglia, including the right anterior putamen. When comparing patients who responded well to clomipramine with those who were either poor or partial responders, we found significant decreases only in the left caudate of patients who responded well to the drug. The present study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms is associated with a return of regional brain metabolism to a more normal level in regions of the orbital frontal cortex and the caudate nucleus.

Adult↗
PubMed1990

Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder. Behavioral and biological results.

Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, double-blind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatment with at least partial benefit were crossed over to fluoxetine treatment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive-compulsive disorder and depressive symptoms that were comparable with precrossover ratings completed during clomipramine treatment. A significant exacerbation in obsessive-compulsive disorder and depression ratings as well as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder. Platelet 5-HT concentrations were reduced 95% during both clomipramine and fluoxetine treatment periods. These results suggest that fluoxetine may represent a viable alternative to clomipramine in the treatment of obsessive-compulsive disorder, although further studies with larger sample sizes are needed.

Adult↗
PubMed1990

Lithium-selective alteration of the function of brain versus cardiac Gs protein.

Lithium was recently demonstrated to inhibit the coupling of both muscarinic cholinergic receptors and beta-adrenergic receptors to pertussis toxin-sensitive and cholera toxin-sensitive G proteins, respectively, thus suggesting alteration of the function of G protein by lithium, as the single site for both the antimanic and antidepressant effects of this drug. One of the most puzzling aspects of the ability of lithium to ameliorate the manic-depressive condition, is its relatively selective action upon the central nervous system (CNS). In the present study, it was shown that lithium selectively attenuated the function of Gs proteins in the CNS, assessed through isoproterenol-induced increases in the binding of guanosine triphosphate (GTP) to these proteins. Therapeutic concentrations of lithium (1-1.5 mM in vitro) inhibited the function of Gs protein in the cerebral cortex of the rat, while 4- to 6-fold larger concentrations of lithium were required to alter the function of Gs protein equivalently in the cardiac ventricles of the rat. Chronic administration of lithium via rat chow, containing lithium carbonate, to rats totally abolished the effect of isoproterenol on the binding of GTP in the CNS but did not affect the function of peripheral cardiac Gs protein. The lithium-selective action on the function of Gs protein in the CNS may stem from the heterogeneity of the alpha s subunit proteins: in the heart, the major species is a 45 kDa molecule, while in the brain, a 52 kDa molecular weight species predominates. The heterogeneity in alpha s subunits may thus be the biochemical basis for the selective action of lithium on the CNS and for the scarcity of peripheral side effects.

Adenosine Diphosphate Ribose↗
PubMed1990

Neuroendocrine, physiologic, and behavioral responses following intravenous nicotine in nonsmoking healthy volunteers and in patients with Alzheimer's disease.

In separate studies, nonsmoking nicotine-naive subjects (11 young and middle-aged normal volunteers and 11 nonsmoking patients with Alzheimer's disease) received up to three doses of intravenous nicotine bitartrate (0.125, 0.25, and 0.5 micrograms/kg/min) and placebo for 60 min. Measurement of plasma ACTH, cortisol, and prolactin showed that nicotine produced in both groups a dose-dependent increase in cortisol, with ACTH in both groups and prolactin in the Alzheimer's group significantly elevated only by the 0.5 micrograms dose. Physiologic measures showed dose-dependent increases that were consistent with previous reports of nicotinic cholinergic stimulation. Behavioral effects included increases in anxiety and decreases in mood, especially following the 0.5 micrograms dose. Physical side effects were modest. The results indicate that nicotinic cholinergic stimulation can activate pituitary hormonal secretion in the human and suggest that nicotinic cholinergic stimulation may constitute an important part of cholinesterase inhibitor-induced endocrine stimulation and behavioral activation.

Adrenocorticotropic Hormone↗
PubMed1990

Marked amine and amine metabolite changes in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

Urinary and plasma amines and amine metabolites were quantified in two individuals with Norrie disease resulting from a deletion in chromosomal region Xp11.3, recently reported to be associated with absence of the gene encoding monoamine oxidase (MAO)-A and nondetectable MAO-A activity in fibroblasts and MAO-B activity in platelets. Marked (four-to 100-fold) elevations in levels of urinary phenylethylamine, o-tyramine, and m-tyramine (which are preferential substrates for MAO-B) and marked reductions (90%) in levels of 3-methoxy-4-hydroxyphenylglycol (a deaminated metabolite of norepinephrine, a preferential substrate for MAO-A) in urine and plasma confirmed the presence of a systemic, functionally significant reduction in the activities of both MAO isozymes. The magnitude of these changes, which are equivalent to those found in subjects taking MAO-inhibiting antidepressants, suggests that early initiation of dietary and drug restrictions may be clinically important in these and other patients with X-chromosomal mutations involving MAO. These findings further support the proposition that the MAOA and MAOB genes are located in close proximity on the X chromosome. Negligible changes in the metabolites of dopamine and serotonin raise the possibility that other metabolic pathways are of importance for their production, that dietary or intestinal bacterial sources contribute substantially to the presence of these amine metabolites in urine, or both.

Adolescent↗