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Biomedical subjects

D L Murphy

Publications and source records attributed to D L Murphy.

At least 271 records · Page 15Linked to original sources
PubMed1988

Intravenous nicotine in Alzheimer's disease: a pilot study.

In the first study to examine direct nicotinic augmentation of central cholinergic functioning in Alzheimer's disease, six patients were studied in an intensive pilot study with three doses (0.125, 0.25, and 0.5 microgram/kg/min) of intravenous nicotine and placebo. Cognitive tests showed a decrease in intrusion errors on the middle (0.25 microgram) dose. Prominent behavioral effects were noted, with significant dose-related increases in anxiety and depressive affect. These results suggest that central nicotinic cholinergic stimulation deserves further investigation as a treatment in Alzheimer's disease and that nicotine may also be a useful investigative tool in other populations as a probe of central cholinergic function, especially in regard to the modulation of affect.

Aged↗
PubMed1988

Fenfluramine-induced suppression of food intake and locomotor activity is differentially altered by the selective type A monoamine oxidase inhibitor clorgyline.

Administration of fenfluramine to rats produced decreases in 1-h food intake and locomotor activity. Short-term (2-6 days) or long-term (21-25 days) treatment with the monoamine oxidase (MAO) type A inhibiting antidepressant clorgyline potentiated fenfluramine-induced suppression of food intake but did not affect fenfluramine-induced suppression of locomotor activity. Although daily (4 h) food intake was not significantly less in clorgyline-treated animals relative to saline-treated controls, body weight gain was significantly less in clorgyline-treated animals relative to controls. These findings demonstrate a differential effect of clorgyline treatment on fenfluramine-induced suppression of food intake and locomotor activity.

Animals↗
PubMed1988

Fawn hooded rats are subsensitive to the food intake suppressant effects of 5-HT agonists.

The food intake suppressant effects of three serotonin agonists, m-CPP (a selective 5-HT1B agonist), 8-OHDPAT (a selective 5-HT1A agonist) and fenfluramine (a 5-HT releasing agent) were compared in three different rat strains: Wistar, Sprague-Dawley (SD) and Fawn-Hooded (FH) rats. Administration of all three serotonin agonists produced dose-dependent decreases in 1 h food intake in all three strains. FH animals were significantly less sensitive to the food intake suppressant effects of all three serotonin agonists than either Wistar or SD rats. Body weight gain over the 9-week course of the study was also significantly less in FH animals than either Wistar or SD animals. These findings support some other data that Fawn Hooded rats, a strain with a peripheral platelet serotonin storage disorder, also possess altered central nervous system serotonergic function.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Effects of fenfluramine, m-chlorophenylpiperazine, and other serotonin-related agonists and antagonists on penile erections in nonhuman primates.

Fenfluramine, m-chlorophenylpiperazine (m-CPP), 1-phenylpiperazine, and the buspirone metabolite, 1-(2-pyrimidyl)piperazine given intravenously to adult rhesus monkeys regularly elicited penile erections. In contrast, serotonin (5-HT) agonists with 5-HT1A site specificity (8-OH-DPAT, buspirone) as well as trazodone, ritanserin, and metergoline were no different from saline in producing penile erections. Fenfluramine's effects were blocked by the 5-HT2 antagonists, ritanserin and metergoline, while m-CPP's effects were not blocked by the peripheral 5-HT antagonist, xylamidine, indicating that tumescence can be elicited by serotonergic agents which act at non-5-HT1A sites in the central nervous system.

Animals↗
PubMed1988

The serotonin agonist, M-chlorophenylpiperazine, markedly increases levels of plasma catecholamines in the conscious rat.

Intravenous administration of the serotonin agonist, m-chlorophenylpiperazine (m-CPP), produced large, dose-dependent increases in epinephrine, norepinephrine and dopamine in plasma in normal, conscious rats. Elevations in the levels of epinephrine, norepinephrine and dopamine (10-fold, 5-fold and 2-fold, respectively) were markedly reduced in pithed and splanchnic denervated rats, suggesting that CNS mechanisms are primarily responsible for the effect of m-CPP on catecholamines in plasma. The serotonin antagonist, metergoline (0.5 mg/kg), decreased the responses of epinephrine and dopamine to m-CPP by 60-80% and also tended to decrease the response of norepinephrine. These findings are consistent with other studies reporting that stimulation of serotonergic receptors increases centrally-mediated sympathetic outflow and leads to increases in the concentrations of norepinephrine, epinephrine and dopamine in plasma.

Animals↗
PubMed1988

A comparison of feeding and locomotion responses to serotonin agonists in three rat strains.

The hyperphagic effects of two selective 5-HT1A agonists (8-OHDPAT and buspirone) in a free feeding paradigm and the locomotor suppressant effect of the serotonin agonist, m-chlorophenylpiperazine (m-CPP) were compared in three different rat strains: Wistar, Sprague-Dawley (SD), and Fawn-Hooded (FH) rats. Administration of various doses of 8-OHDPAT and buspirone produced significant increases in two-hour food intake only in Wistar and SD strains and not in the FH strain. Similarly, various doses of m-CPP produced significant decreases in locomotor activity only in Wistar and SD strains and not in the FH strain. Isolated FH animals gained significantly less body weight relative to both Wistar and SD animals. These findings demonstrate attenuated feeding and behavioral responses to serotonergic agonists in the FH strain relative to both Wistar and SD strains.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Long-term imipramine treatment differentially affects fenfluramine-induced suppression of food intake and locomotor activity.

Administration of fenfluramine to rats produced decreases in one-hour food intake and locomotor activity. Short-term (2-6 days) or long-term (21-25 days) treatment with the tricyclic antidepressant, imipramine, did not affect daily food intake, body weight gain or baseline locomotor activity when compared to saline treatment. However, long-term but not short-term imipramine treatment attenuated fenfluramine-induced decreases in one-hour food intake. On the other hand, neither short-term nor long-term imipramine treatment affected fenfluramine-induced decreases in locomotor activity. These findings demonstrate a differential effect of long-term imipramine treatment on fenfluramine-induced suppression of food intake and locomotor activity.

Animals↗
PubMed1988

The effect of 8-OH-DPAT on temperature in the rat and its modification by chronic antidepressant treatments.

Administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to rats produced a dose-dependent hypothermia. Pretreatment with the receptor antagonist methiothepin abolished this effect, and pretreatment with haloperidol, propranolol and pindolol partially attenuated it, although methiothepin and pindolol had hyperthermic actions of their own. Other receptor antagonists including ritanserin, naloxone, clonidine, phenoxybenzamine and metergoline did not significantly modify the response elicited by subsequent 8-OH-DPAT challenge. In antidepressant studies, chronic treatment (22 days) with clorgyline attenuated the hypothermic response to 8-OH-DPAT, whereas similar duration of treatment with the tricyclics clomipramine and imipramine did not significantly modify it. Also, acute treatment for three days with each of the antidepressants did not modify 8-OH-DPAT-induced hypothermia. We conclude that rat rectal temperature can be a useful model to help assess the functional state of serotonergic mechanisms, including the adaptational changes induced by long-term antidepressant treatment.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Induction of migrainelike headaches by the serotonin agonist m-chlorophenylpiperazine.

In a study of serotonin (5-HT) function in patients with eating disorders and healthy control subjects, severe headaches with features of common migraine occurred unexpectedly in 28 of 52 subjects (54%) 8 to 12 hours after receiving a single oral dose of the 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg. None of the same subjects developed similar late-occurring headaches after placebo or the 5-HT precursor, L-tryptophan, 100 mg/kg given intravenously. The frequency of these migrainelike headaches was not significantly different between patients with bulimia or anorexia nervosa and control subjects, but incidence of headaches was significantly greater in subjects with a personal or family history of migraine, with almost all predisposed individuals (18 of 20, 90%) developing severe symptoms. Headache ratings were also significantly correlated (rho = 0.70; p less than 0.0001) with peak concentrations of m-CPP in plasma. These observations indicate that m-CPP may provide a novel probe for studies of the pathophysiology of migraine headaches.

Adult↗
PubMed1988

High-dose naloxone in older normal subjects: implications for Alzheimer's disease.

The behavioral and cognitive effects of naloxone HCl, in doses of 5 micrograms/kg, 0.1 mg/kg, and 2.0 mg/kg administered as an IV bolus, were assessed in a double-blind, placebo-controlled, randomized study of eight normal subjects ranging in age from 44 to 74 years (mean 63). Naloxone produced mild behavioral effects with slight cognitive impairment after the 2.0 mg/kg dose only. The threshold, dose dependency, characteristics, and magnitude of these behavioral effects were similar to what has previously been reported in young normal subjects, but markedly different from those observed in patients with dementia of the Alzheimer type (DAT) matched in age to the current study sample. These data suggest that the metabolic fate of naloxone is not substantially affected by age within the range studied. The findings of this study provide further support for a role for endogenous opiate systems in the modulation of behavior and cognition, and suggest that the unusual behavioral sensitivity of patients with DAT to naloxone cannot be accounted for by the effect of age.

Adult↗
PubMed1988

Differential neuroendocrine responses to the 5-HT agonist m-chlorophenylpiperazine in Fawn-Hooded rats relative to Wistar and Sprague-Dawley rats.

The effect of various doses of the 5-HT agonist m-chlorophenylpiperazine (MCPP) on neuroendocrine function (prolactin and corticosterone responses) were compared in three different rat strains: Wistar, Sprague-Dawley (SD), and Fawn-Hooded (FH) rats. Administration of various doses of MCPP produced increases in plasma concentrations of prolactin and corticosterone in all three rat strains. The prolactin responses of FH rats to MCPP were significantly smaller than that of either Wistar or SD rats, while corticosterone responses were equivalent across all three strains. On the other hand, baseline concentrations of corticosterone, but not of prolactin, were significantly higher in FH animals relative to both Wistar and SD animals. There was no significant difference in either baseline hypothalamic concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, or dopamine or brain concentrations of MCPP among these three rat strains. These findings support some other data indicating that FH rats, a strain with a peripheral platelet serotonin storage pool disorder, also possess alterations in some neuroendocrine functions which are modulated by serotonin.

Animals↗
PubMed1988

Return of symptoms after discontinuation of clomipramine in patients with obsessive-compulsive disorder.

To evaluate the need for maintenance drug therapy in patients with obsessive-compulsive disorder, the authors assessed 21 patients with obsessive-compulsive disorder who manifested sustained improvement during 5 to 27 months of clomipramine treatment and who agreed to participate in a double-blind discontinuation study. Of 18 patients who completed the study, 16 had substantial recurrence of obsessive-compulsive symptoms by the end of the 7-week placebo period. In addition, 11 had a significant increase in depressive symptoms. Treatment duration before discontinuation of clomipramine was not related to the frequency or severity of obsessive-compulsive or depressive symptom appearance. These findings suggest that prolonged drug treatment may be warranted for obsessive-compulsive disorder.

Adult↗
PubMed1988

Tranylcypromine compared with L-deprenyl in Alzheimer's disease.

The authors have previously reported mild improvement of behavior and cognition in a group of 17 nondepressed patients with dementia of the Alzheimer type (DAT) treated with two doses of L-deprenyl (10 and 40 mg/day). Seven of these patients subsequently received double-blind, placebo-controlled treatment with tranylcypromine. The patients experienced significant side effects, particularly orthostatic hypotension without compensatory pulse increase, during tranylcypromine treatment. These effects were more severe than those occurring during L-deprenyl treatment, and they occurred at substantially lower doses (mean dose, 16 mg/day). These data support the role of the inhibition of monoamine oxidase type A in the development of orthostatic hypotension in patients treated with monoamine oxidase inhibitors. They also raise the question of whether the observed sensitivity to monoamine oxidase inhibition is a function of age or disease. In either case, the greater toxicity of tranylcypromine makes inferences difficult regarding the relative efficacies of these drugs in treating patients with dementia of the Alzheimer type and may limit the potential usefulness of tranylcypromine in ameliorating some symptoms of this disease.

Aged↗